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2020
Paths of Research and Care
Progress at Dana-Farber
Cancer Institute
Machine Learning:
Bringing Artificial Intelligence
into Personalized Cancer Care
PLUS:
A Case For Curiosity: Dr. Kaelin’s Path to the 2019 Nobel Prize
Liquid Biopsies
Dana-Farber’s 2019 Annual Report
TABLE OF CONTENTS
2020 Volume 27, Number 1
14
8 22
FEATURES DEPARTMENTS
8 A Case for Curiosity 2 Around the Institute
Tracing the circuitous path that led to the 2019 Nobel News and highlights from Dana-Farber, with a salute
Prize in Physiology or Medicine for Dana-Farber’s to care teams responding to the COVID-19 crisis.
William Kaelin Jr., MD.
32 Why I Work Here: Ildemaro Gonzalez
14 Unexpected Benefits from Targeted Therapies Dana-Farber Vice President and Chief Inclusion and
New research shows that CDK 4/6 and PARP Inhibitors Diversity Officer describes what drives his work.
can stimulate the immune system to fight cancer, in
33 Questions for Marilyn Hammer, PhD, RN
addition to their known effects in fighting tumor cells.
A closer look at nursing science and how it can
18 Shapeshifters in the Brain improve patient care.
Understanding how aggressive brain tumors evade
treatment with new technology that examines genetic 34 Dana-Farber 2019 Annual Report
information within individual cells, one at a time.
22 Bringing AI to Personalized Cancer Care
Machine language technology brings the new
capability to study each individual’s risks and best
treatment options.
28 Liquid Biopsies Move Toward the Clinic
Chemical biologists create small molecules to boost
discoveries and prototype novel therapies.
Vis it D a na - Fa r be r o n l i n e. www. d an a-far b er. o r g
Paths of Progress is published by Dana-Farber Cancer Institute.
Copyright © 2020 Dana-Farber Cancer Institute. All rights reserved.
PRESIDENT’S LETTER
DEAR READERS
Ordinarily during March and April, we’d be preparing to share
with you this in-depth look at our research and clinical advance-
ments. But those ordinary times were quickly swept away and,
understandably, our focus at the Institute turned to confronting
the COVID-19 pandemic.
Our staff has responded admirably to the unprecedented chal-
lenges posed by this public health crisis. Their talent, tenacity, and
dedication to keep our patients safe and supported has been nothing
short of heroic. Certainly, we recognize that our patients’ cancers
will not slow or wait for this pandemic to pass. And we have taken
every possible measure to continue to be a steady source of hope
and healing to our patients and families during this difficult time.
I also recognize that despite the extraordinary circumstances and
uncertainty that surrounds the outbreak, this remains a revolutionary
time for cancer care and scientific discovery, and we can ill afford to
lose any progress. By taking the appropriate safety measures to limit
the number of staff working on site and transitioning many to remote
work, we are moving forward with our bold research mission, and
continuing to see patients, both in person at the Institute, and virtu- “Our staff has responded admirably to
ally through expanded telemedicine options. This allows us to see
the unprecedented challenges posed
thousands of new people each week, signaling to cancer patients
everywhere that, as always, and especially in a time of crisis, we by this public health crisis. Their
are here for them. talent, tenacity, and dedication to
The articles in this issue of Paths of Progress shed more light on
the progress that we continue to make in spite of these extraordi- keep our patients safe and supported
nary obstacles. It covers work that began long before the onset of has been nothing short of heroic.”
COVID-19 and will continue long after it recedes. For as daunting this
experience has been for all of us, I need not look any further than
– Laurie H. Glimcher, MD
our own patients as a constant reminder of why our work and mis-
sion remain critically important. The coronavirus poses its own risks
and challenges to patients facing cancer. And they look to us for
relief, support, and hope. I look forward to the day when this crisis is
behind us and we can focus singularly on the limitless possibilities to
find new cures and new hope for our patients, as we have through-
out Dana-Farber’s long history.
Laurie H. Glimcher, MD
President and CEO, Dana-Farber Cancer Institute
AROUND THE INSTITUTE Saverin Family Gift Provides $20 Million for Metastatic Breast Cancer Research A $20 million gift to Dana-Farber from the Saverin or lungs. It is a treatable but currently an incurable Family last year established the new Saverin form of breast cancer. Breast Cancer Research Fund under the direc- A world-renowned leader in the breast cancer tion of Eric Winer, MD, senior vice president for field, Winer has made seminal contributions to medical affairs, chief of Breast Oncology in the improve the treatment of this disease, with a focus Susan F. Smith Center for Women’s Cancers, and on the aspects of breast cancer that remain the the Thompson Chair in Breast Cancer Research most challenging. at Dana-Farber. The commitment is the largest “The Saverin Family’s foresight will allow individual gift for breast cancer research in Dana- us to tackle the unsolved challenges by building Farber’s history. on the advances we have already forged, The sole purpose of the Saverin Family’s gift and to develop entirely new strategies,” is to support research relating to treatment and said Winer. “Their exceptional generosity eventual cures of advanced or stage IV metastatic provides resources we need to further breast cancer. Metastatic breast cancer is cancer metastatic breast cancer research that is that has spread outside of the breast and to other underway, and, more importantly, to open bold parts of the body, such as the bones, brain, liver, avenues of investigation.” Dana-Farber Establishes Riney Family Multiple Myeloma Initiative Dana-Farber this year started the Riney Family this initiative provides an opportunity to acceler- Multiple Myeloma Initiative to help improve out- ate the most promising strategies and meaningfully comes and accelerate understanding of the underly- extend remissions.” ing biology for the most challenging types of myelo- Rodger Riney was diagnosed with multiple myelo- mas, cancers that form in a type of white blood cell ma in 2015 and treated at the Washington University called a plasma cell. The initiative is being estab- School of Medicine and Siteman Cancer Center at lished with a $16.5 million gift from Paula and Rodger Barnes-Jewish Hospital. In 2018, Ken Anderson, MD, Riney of St. Louis, Missouri. program director at Dana-Farber’s Jerome Lipper The gift from the couple’s foundation, the Paula Multiple Myeloma Center and LeBow Institute for and Rodger Riney Foundation, is the largest single Myeloma Therapeutics and Kraft Family Professor gift from a family to support multiple myeloma can- of Medicine at Harvard Medical School, joined as an cer research and care in Dana-Farber’s history. The advisor to Riney’s care team. Riney Family Multiple Myeloma Initiative at Dana- “As a myeloma patient, you are very aware Farber will add to their legacy of multiple myeloma of the groundbreaking work being done at support, and will improve outcomes for myeloma Dana-Farber in multiple myeloma,” said Riney. patients everywhere. “Dana-Farber is an institution we want to invest “We are deeply grateful to the Riney Family for this in given its impressive track record in improving inspired gift that will quickly advance our knowledge myeloma treatment. Our hope is that this gift will of multiple myeloma,” said Laurie H. Glimcher, MD, inspire others to support Dana-Farber’s researchers president and CEO, Dana-Farber. “While we have and clinicians to extend survivorship, and ultimately made significant strides in treating multiple myeloma, find a cure.” 2 Paths of Progress 2020 Dana-Farber Cancer Institu te
AROUND THE INSTITUTE
Largest-Ever Gift for Glioblastoma Research Aims to
Address Obstacles
Dana-Farber/Brigham drug development, and and Alexandra Golby, zations. This gift is
and Women’s Cancer palliative care. MD, director of image- a way to give back to
Center (DF/BWCC) Jonathan Oppen- guided neurosurgery. the physicians who
announced in 2019 a heimer made the gift in “My family and I are took care of her while
groundbreaking gift memory of his late wife, grateful for the kind and also honoring and car-
from Oppenheimer Jennifer Oppenheimer, expert care Jennifer rying forth her work
Generations Foundation who passed away from received at DF/BWCC to help others.”
to create The Jennifer glioblastoma in May during the most chal- The Jennifer
Oppenheimer Cancer 2017. During her illness, lenging and difficult Oppenheimer Cancer
Research Initiative. Jennifer was treated time of our lives,” says Research Initiative
This translational by David Reardon, MD, Jonathan. “Jennifer is the Oppenheimer
research initiative will clinical director of the was a powerful and family’s first major
address key obstacles Center for Neuro-Oncol- vibrant force for good gift to DF/BWCC
across the continuum ogy, James Tulsky, MD, who touched the lives and is the largest
of care facing patients chair of the department of thousands through individual gift to glio-
with glioblastoma — of Psychosocial Oncol- her extensive advocacy blastoma research in
including surgery, new ogy and Palliative Care, for civil society organi- DF/BWCC’s history.
Dana-Farber Lab Focuses on Pancreatic Cancer Research
Dana-Farber has been given another tool in the In the last 20 years, the Lustgarten Foundation
fight against pancreatic cancer. Thanks to a $5 mil- has given more than $10 million to Dana-Farber for
lion grant from the Lustgarten Foundation, the Insti- pancreatic cancer research.
tute established a new pancreatic cancer research
laboratory in the Hale Family Research Center. The
dedicated lab is one of two new facilities funded
by the Lustgarten Foundation – the second is located
at MIT.
Dana-Farber’s Lustgarten Foundation Pancreatic
Cancer Research Laboratory is led by Brian Wolpin,
MD, MPH, director of the Hale Family Research
Center and the Robert T. and Judith B. Hale Chair
in Pancreatic Cancer, whose research focuses on
personalizing therapy and identifying new ways to
detect pancreatic tumors earlier.
“You need individuals and institutions who will
support your work and push you to be better,” said
Wolpin during a ribbon-cutting ceremony in Septem-
ber 2018. “Thanks to the funding from the Lustgarten
Foundation, we will have additional support to make
a difference for patients with pancreatic cancer.” Brian Wolpin, MD, MPH
www.dana-farber.org 3
AROUND THE INSTITUTE
Dana-Farber Establishes Chen-Huang Center for EGFR Mutant
Lung Cancers
Dana-Farber in 2020 created the Chen-Huang Center
for EGFR (epidermal growth factor receptor) Mutant
Lung Cancers to stimulate research, promote clinical
trials, and strengthen the Institute’s capabilities for
studying and treating lung cancers driven by EGFR
gene mutations. The Chen-Huang Center was estab-
lished with a $5 million gift from Winston Chen, PhD,
and his wife, Phyllis Huang, of Silicon Valley.
Pasi Jänne, MD, PhD
For many years, the couple’s family foundation, the
Paramitas Foundation, had focused on supporting More than 200,000 people in the U.S. and more than
higher education. Their recent funding has shifted to one million worldwide were diagnosed with lung cancer
health care projects, specifically lung cancer care and in 2019. Lung cancer remains the most common cause
research led by Pasi Jänne, MD, PhD, director of the of cancer-related deaths for both men and women in
Carole M. and Philip L. Lowe Center for Thoracic Oncol- the U.S. EGFR mutations are found in 15% of patients in
ogy, and director of the Robert and Renée Belfer Center the U.S. and European Union, and 50% of lung cancer
for Applied Cancer Science at Dana-Farber. patients in Asia.
“Phyllis and I hope our gift will bring much needed “This generous gift will allow us to further push the
attention to lung cancer and illustrate how vital financial boundaries of knowledge in this area to eventually de-
support is for making discoveries,” said Chen. “We sup- velop new and better therapies,” said Laurie H. Glimcher,
port Dr. Jänne and Dana-Farber because of their impres- MD, president and CEO, Dana-Farber. “We are very
sive centers, research facilities, and the discoveries they grateful to Winston Chen and Phyllis Huang for their
are making every day.” support to create this new center.”
Gift Creates the Edward P. Evans Center for
Myelodysplastic Syndromes
A $5 million gift to Dana-Farber from the Edward current cure for MDS is a stem cell (bone mar-
P. Evans Foundation enabled the creation of the row) transplant from a healthy donor, but currently
Edward P. Evans Center for Myelodysplastic Syn- fewer than 10% of patients with MDS are able to
dromes (MDS). The gift will help Dana-Farber in undergo transplant due to advanced age or other
transformative collaborative research aimed at medical problems.
treating, preventing, and ultimately curing MDS. “The Edward P. Evans Center for MDS at Dana-
MDS are a group of diseases in which the bone Farber will be a nexus for discoveries in MDS
marrow makes too few healthy blood cells. Patients and improvements in patient care that will help
with MDS often suffer from debilitating fatigue reduce the global burden of MDS,” said Laurie H.
and may require regular blood transfusions. Some Glimcher, MD, president and CEO of Dana-Farber.
patients with MDS are also at risk for infection or “We are deeply grateful and encouraged by the
bleeding due to low white blood cell count or platelet support from the Edward P. Evans Foundation and
count, and at least 20% of patients with MDS will are thrilled to provide a platform to support inves-
develop acute myeloid leukemia (AML). The only tigators at every level.”
4 Paths of Progress 2020 Dana-Farber Cancer Institute
AROUND THE INSTITUTE
Volunteers Support Patients and Staff from Home
Caitlin Geaney loved her first few COVID-19 forced her to step away says Pat Stahl, senior manager of
months volunteering with Dana- from her volunteer shifts and she saw Volunteer Services and Programs
Farber’s Ambassador Program, similar efforts on social media. at Dana-Farber. “They’ve kept our
guiding patients and other Yawkey “Volunteering is something I always community together.”
Center visitors to appointments look forward to. I saw it as a time Dana-Farber has nearly 500 volun-
and resources. But the COVID-19 when I could make a difference,” teers in a variety of roles. While
crisis left her unable to provide such says Geaney. “This [project] was a restricted from visiting campus dur-
assistance in-person, so Geaney way to do that from home.” ing the COVID-19 crisis, they con-
found other ways to show the Many of her colleagues felt the tinued to help remotely. Volunteers
Dana-Farber community that she same way. Dozens of volunteers, helped patients learn to use video-
and other volunteers are thinking most of whom she’d never met, sent conferencing apps for telehealth
of them. Geaney photos of themselves holding appointments, ran online workshops,
A 21-year-old student at the signs. Geaney designed a collage and even formed an online book club.
Massachusetts College of Phar- with the photos and added a message “It is incredible how fast our
macy and Health Sciences, Geaney of thanks. The finished poster was volunteers have adapted,” says
spearheaded the Gratitude Project shared with Dana-Farber patients and Maritza Nassif, program coordinator
– a photo collage of volunteers staff via email and social media. for Patient and Family Services.
holding messages of support and “It shows the level of dedication “They have made it clear they want
thanks. She hatched the idea when people have for their volunteer roles,” to stay involved.”
Keeping the Jimmy Fund Clinic a Place to Smile
Dana-Farber’s Jimmy Fund Clinic in April 2020 Shea, BSN, RN, an infusion nurse in the clinic, from
looked completely different than it did just a few joining her colleagues to show off a few dance
weeks before, with events postponed, fewer visitors, moves while a patient played the role of DJ from an
and all staff required to wear masks – making it im- infusion chair.
possible to see the smiles that usually greet patients “We’re still acting silly and crazy,” says Shea.
entering the clinics. But behind each mask is still the “It’s all about staying positive, taking it one day at
friendly face of someone available to talk through a a time, and focusing on what the patient needs at
difficult time or break out an impromptu dance party that moment.”
just to make a patient grin. That’s important, because
despite the unprecedented challenges of COVID-19,
the Jimmy Fund Clinic is still providing treatment to
patients who need to undergo weekly, or even
daily therapy.
“We’re working to be the one constant in our
patients’ lives,” says Lisa Scherber, director of Patient
and Family Programs at Dana-Farber/Boston Chil-
dren’s Cancer and Blood Disorders Center. “Everyone
has been incredibly resilient, and it’s important we
provide a sense of normalcy for them.”
For example, social distancing didn’t stop Courtney Dana-Farber’s Jimmy Fund Clinic
www.dana-farber.org 5
AROUND THE INSTITUTE
Saluting our Staff During
6 Paths of Progress 2020 Dana-Farber Cancer Institu te
AROUND THE INSTITUTE
the COVID-19 Pandemic
www.dana-farber.org 7
A C AS E F O R 8 Paths of Progress 2020 Dana-Farber Cancer Institu te
CURIOSITY
BY ROBERT LEVY
www.dana-farber.org 9i
n a pragmatic, goal-oriented a course of research wherever
age, the notion of curiosity it led, it would be unwise to bet
as the driving force behind against its potential.
research might seem out of Long before the morning he
fashion. But in the long run, learned he had co-won medi-
it may be curiosity – unim- cine’s highest award, Kaelin,
peded and open-minded – the Sidney Farber Professor of
that cures cancer. Medicine at Dana-Farber and
For evidence, one need Harvard Medical School, senior
look no further than the physician in Medicine at Brigham
2019 Nobel Prize in Physiology or and Women’s Hospital, and
Medicine, awarded to Dana-Far- Howard Hughes Medical Institute
ber’s William Kaelin Jr., MD, Sir investigator, has been making the
Peter Ratcliffe of the University of case for curiosity-driven research
Oxford, and Gregg Semenza, MD, and its potential to transform the
PhD, of Johns Hopkins Univer- treatment of disease.
sity. At the outset, it was far from “The beauty, as well as the
obvious that Kaelin’s work would challenge, of basic science is that
contribute to a pivotal discovery you can’t always predict what the
about how cells adapt to changes outcome of the work is going to
in oxygen levels. But because it be,” he says. “You’re investing in
sprang from a desire to answer the creation of new knowledge,
a fundamental biological ques- and the only thing you can be
tion, and a willingness to follow sure of is that the more you invest
in basic science, the more new
knowledge you will generate.
And the more knowledge we
have, hopefully, the more im-
provement we will have in the
quality of our lives.”
The Right Spot
Choosing an area of research is,
Kaelin likes to say, like fishing: It’s
ultimately guesswork, but guess-
work informed by experience and
a sense of where the greatest
promise lies. As a budding labora-
tory scientist in the early 1990s,
he was looking for something that
was interesting not only in itself
but as a source of clues into a vari-
ety of cancers – something where
research could be informative as
well as impactful.
William Kaelin Jr., MD, at his whiteboard. The answer came in 1993 when
10 Paths of Progress 2020 Dana-Farber Cancer Institu tehe read a report in Science maga- It was the last of these possibil- send out distress signals that spur
zine about the cloning of a gene ities that would yield discoveries the formation of red blood cells
called VHL. “The moment I saw deserving of a Nobel Prize. and blood vessels. Understand-
the paper I said, this is perfect, ing how cancer cells hijack the
this is what I should work on,” A Monopoly on Oxygen hypoxia response would be a
Kaelin relates. At first, it might seem that ques- first step toward blocking it – and
The gene met Kaelin’s criteria tions about cells’ capacity for potentially starving the cells of a
for a subject at the hub of mul- adjusting to changes in oxygen fuel they need to survive.
tiple questions in cancer. People have more to do with mountain- By the late 1990s, several lines
with a mutated, or abnormal, VHL climbing than malignancy. In virtu- of research were zeroing in on
gene are at high risk of develop- ally all animals, oxygen is needed cells’ machinery for gauging
ing a rare disorder called von to convert food energy into a changes in oxygen levels and
Hippel-Lindau (VHL) syndrome useful form. When the demand adjusting to them. Kaelin’s group
in which tumors and cysts form for oxygen exceeds the available had theorized that the VHL gene
in multiple organs and tissues. supply – at high elevations, for was involved in oxygen sensing:
Although some of these growths
are benign, they can be harmful
if they press on or interfere with “The beauty, as well as the challenge, of basic
neighboring tissues. Some of the science is that you can’t always predict what
tumors, such as kidney cancers,
are malignant and can spread to the outcome of the work is going to be.”
other parts of the body. Research
into the disorder offered a way to
– Willam Kaelin Jr., MD
help patients and, Kaelin intuited,
generate broader insights. Scien-
tists quickly determined that the example, or during exercise – the the fact that VHL tumors are laced
VHL gene also plays a critical role body responds by ramping up pro- with blood vessels and laden with
in non-hereditary kidney cancer. duction of red blood cells (which red blood cells suggested that
Kaelin thought that studying the carry oxygen by binding it to when the gene is mutated, the
VHL gene might provide important hemoglobin), building new blood sensing mechanism is broken.
insights into the common form vessels (to channel more blood To test the theory, they created
of cancer. cells to tissue), and activating gly- human kidney cancer cell lines
Because tumors associated colysis (a series of reactions that that were identical except that
with VHL disease are often rich extract energy from blood sugar). one had a normal version of the
in blood vessels, studying them A variety of diseases can prompt VHL gene and the other didn’t.
could also help explain how the body to take these steps, They grew them in either a high-
tumors reroute the bloodstream known as the hypoxia response, or low-oxygen environment and
for nourishment. And because even though environmental levels looked for the presence of RNAs
people with VHL tumors can of oxygen are normal – stroke, that normally are produced only
develop a sharp increase in red heart disease, anemia, infection, when oxygen levels are low.
blood cell production – normally and, perhaps surprisingly, cancer. “My jaw dropped when I saw
a sign that tissues aren’t getting Cancer cells are hoarders at the results,” Kaelin recalls.
enough oxygen – VHL research the bloodstream’s banquet of “We found that cells without the
could shed light on how cells nutrients. To fuel their breakneck- normal VHL gene overproduced
sense and respond to changes growth, they demand an extra those RNAs whether oxygen
in oxygen levels. helping of oxygen. To get it, they was present or not. It confirmed
www.dana-farber.org 11“Now that we’ve mapped the molecular pathway are high, a protein complex called
HIF-1 is steadily eroded, but when
behind the hypoxia response, we have clues they’re low, HIF-1αbuilds up. The
discovery quickly converged with
about where to intervene to make the pathway Kaelin’s work. In 2001, Kaelin and
Ratcliffe independently showed
more or less active.”
that under normal oxygen con-
ditions, cells place a chemical
– William Kaelin Jr., MD tag on HIF-1, prompting the VHL
protein to destroy it. When VHL is
that the gene was required for ers didn’t know precisely how missing or deformed because of
oxygen-sensing.” changes in oxygen flipped this a genetic mutation, HIF-1αdoesn’t
This finding, from 1996, was molecular switch. Semenza had get degraded, causing the cell
a major advance, but research- found that when oxygen levels to act as though oxygen levels
are low.
The sense of curiosity that
drove the researchers had
brought them to a molecular
mechanism that was itself a
rather curious bit of cellular
operations. The HIF-1αcomplex
functions, in a way, like a reverse
thermometer: when oxygen levels
are adequate, HIF-1αrecedes;
when the levels drop, HIF-1α rises,
ordering delivery of a kind of oxy-
gen mask to cells gasping for air.
Coming to the Clinic
Following the 2001 break-
through, Kaelin, Semenza, and
Ratcliffe uncovered more details
of the oxygen-response system
William Kaelin Jr., MD, in his lab. and showed that malfunctions in
William G. Kaelin Jr., receives his MD Joins Dana-Farber as a clinical fellow Becomes an independent investiga-
from Duke University. Publishes his first in Medical Oncology and a year later tor at Dana-Farber. A key focus of his
research paper as a first author, on the becomes a postdoctoral fellow in the research is von Hippel-Lindau (VHL)
effect of the drug verapamil on blood laboratory of David Livingston, MD, disease, a rare, hereditary disorder
flow in normal and tumor tissue. where he begins his studies of tumor marked by the formation of tumors and
suppressor genes. cysts in different parts of the body.
1982 1988 1992
12 Paths of Progress 2020 Dana-Farber Cancer Institu tethe system can play a role in can-
cer and other diseases. Kaelin, for
example, found that a defect in
HIF-2α– a close kin of HIF-1α–
propels the growth of certain
kidney cancers and that triple-
negative breast cancers often
make use of HIF-1α.
Researchers are also working
on practical applications of their
discoveries. “Now that we’ve
mapped the molecular pathway
behind the hypoxia response, we
have clues about where to inter-
vene to make the pathway more
or less active,” Kaelin remarks.
“For example, we now have
drugs that prevent HIF-1αfrom de-
teriorating, which might be useful
for diseases like anemia, heart
attack, and stroke, where oxygen
delivery is problem. Conversely,
blocking the pathway, with HIF-2α William Kaelin Jr., MD, describes his research at a press conference.
inhibitors, for example, looks like
a promising way to treat kidney science doesn’t exist to satisfy “Some people might think it
cancer. I’m also hopeful that HIF- curiosity but to perpetuate it – risky to have talented scientists
1αinhibitors might be useful for that discoveries are not goals follow only their curiosity, because
certain cancers.” as much as they are incentives we won’t necessarily be able to
The Nobel Prize win has to pursue more research. At the predict where the road will take
amplified Kaelin’s challenge to most basic level, curiosity-driven them and we won’t be able to pre-
those who believe curiosity- research is an expression of dict what the fruits of their labors
based research is too unreliable confidence in the mind’s ability will be,” Kaelin asserts. “But we
to undertake or invest in. From to make connections, perceive know, over and over, that’s how
experience, Kaelin knows that promise, and inspire others. real progress happens.”
Shows that cells lacking correct cop- Kaelin and British scientist Peter Named co-recipient of the Nobel Prize
ies of the VHL gene are incapable of Ratcliffe independently uncover a in Physiology or Medicine, together
sensing oxygen – an important clue in critical piece of cells’ oxygen-sensing with Ratcliffe and Greg Semenza, for
understanding how cells detect and mechanism, showing how cells “know” discovering how cells sense and adapt
adjust to changes in oxygen levels. whether oxygen is available. to changes in oxygen.
1996 2001 2019
www.dana-farber.org 13Unexpected
Benefits from
Targeted Therapy
How CDK4/6 and PARP inhibitors work
together in targeting disease
BY ROBERT LEVY
S
erendipity is rarely sweeter than when it occurs in cancer research. In a field where progress is
hard-won, where success often comes in increments rather than wholesale leaps, it’s particularly
rare for a new treatment to not only work as intended but also to possess powers that developers
hadn’t expected.
Yet that is precisely what narrow-gauge attack on cancer from the time they entered clinical
Dana-Farber researchers recently cells – may do double duty as trials. They were first approved by
discovered about two of the immunotherapies. the Food and Drug Administration
most effective types of targeted (FDA) in 2015 for patients with the
therapies – CDK4/6 inhibitors Alternate Tracks most common subtype of breast
and PARP inhibitors – to arrive PARP inhibitors and CDK4/6 cancer (hormone receptor-positive
in recent years. The twin find- inhibitors target cancer cells by breast cancer) and are currently
ings, announced within months of two very different routes. being tested, with encourag-
each other, show that in addition CDK4/6 inhibitors, which have ing results, in a variety of other
to having their known effects in a long pedigree in Dana-Farber cancers. “In early trials of these
tumor cells, the agents also can research, deprive cancer cells of drugs, we noticed that in some
stimulate the immune system to their most notorious characteris- breast cancer patients the tumors
fight cancer. The findings suggest tic: their ability to divide endlessly. didn’t just remain the same size –
that, effective as the drugs are They work by blocking enzymes as would be expected with drugs
on their own, they could be even needed to pass from one phase that interfere with cell division –
more potent when combined with of the cell cycle to the next. The but began to recede, sometimes
agents that release barriers to the result is something very un-cancer- quite dramatically,” said Dana-
immune response. like – a tumor cell that simply Farber’s Shom Goel, MD, PhD.
Together, the discoveries sug- vegetates, that survives without The reason for the shrinkage,
gest that many targeted thera- growing or proliferating scientists at Dana-Farber and
pies – usually thought to wage a The drugs showed promise Brigham and Women’s Hospital
14 Paths of Progress 2020 Dana-Farber Cancer InstituteIllustration of a T lymphocyte
cell attached to a cancer
cell. T lymphocytes are a
type of white blood cell
that recognizes a specific
site (antigen) on the surface
of cancer cells or pathogens
and bind to it. Some
T lymphocytes then signal
for other immune system
cells to eliminate the cell.
(BWH) found, lay outside the cell- mount an attack on the tumors – a to reveal their malignant nature by
division machinery itself, in the finding they confirmed by analyz- decking themselves in abnormal
cancer’s always delicate relation- ing tissue samples from women in proteins called neoantigens. The
ship with the immune system. a clinical trial of a CDK4/6 inhibitor immune system, incited by this
Leading the research with Goel for breast cancer. display, responds by attacking
were Hye-Jung Kim, PhD, working The drugs trigger an anti-tumor the tumor cells. At the same time,
the laboratory of Jean Zhao, PhD, immune response in two ways, the drugs cause the number of
of Dana-Farber and the Broad the researchers reported in “T regulatory cells,” or Tregs,
Institute of MIT and Harvard, and Nature. They prompt tumor cells to diminish. These cells, the
Molly DeCristo, a Harvard Medi-
cal School graduate student in the
laboratory of Sandra McAllister,
“In early trials of these drugs, we noticed that in
PhD, at BWH. some breast cancer patients the tumors didn’t just
To understand why the tumors
sometimes shrank, the investiga- remain the same size – as would be expected
tors examined how the CDK4/6
inhibitor abemaciclib acted in with drugs that interfere with cell division – but
animal models of breast or other
solid tumors. They found it not began to recede, sometimes quite dramatically.”
only stalled the tumor cycle but
also caused the immune system to – Shom Goel, MD, PhD
www.dana-farber.org 15“We’ve shown that in the case of ovarian cancer, Mutations or
other genetic
another factor is at play – the effects of the abnormalities
can disable
drugs on the interaction of tumor cells with proteins involved
the immune system.” in making such
repairs. As the
damage mounts,
– Jean Zhao, PhD the cell’s abil-
ity to function
pacifist cousins of the better- nections between CDK4/6 inhibi- – dependent on
known “killer” T cells, exert a tors and the immune response. the instructions
sedating effect on the immune One showed that the drugs cause encoded in its
response to disease or infection. tumor cells to sprout additional DNA – diminish-
With fewer Tregs in circulation, PD-L1 proteins on their surface. es, potentially to
the immune response intensi- These proteins ordinarily allow the point where
fies. Taken together, these two tumor cells to derail an immune it can no longer
processes have the ability to halt attack, suggesting that combin- sustain itself.
or even reverse tumor growth. ing CDK4/6 inhibitors with drugs PARP in-
Within a few months of the that foil PD-L1 could leave tumors hibitors take
publication of these findings, two especially vulnerable to the advantage of
other research teams including immune response. The second this weakness by administer-
Dana-Farber scientists published paper showed that CDK4/6 inhibitors ing a finishing blow to cancer
papers that found additional con- also “activate” immune system cells. Cells with mutations in the
T cells, putting them in BRCA genes, for example, have
attack mode against trouble repairing breaks that
cancer cells. occur in both strands of the DNA
molecule. They compensate, in
Picking at a Sore part, by relying on genes that
PARP inhibitors, the mend breaks in one strand. PARP
second category of inhibitors work by crippling some
ILLUSTRATION BY JULIA GLUYAS
CDK4/6 PARP targeted drugs with an of those single-strand specialists.
Inhibitors Inhibitors immune-stimulating Already coping with the loss of
Halt Cancer Hinder DNA Repair side, work by taking a two-strand repair genes, the cells
Cell Division in Cancer Cells
common vulnerability in are ready prey for drugs that shut
cancer cells and aggra- down the single-strand repair
Both Stimulate an Immune
vating it even further. machinery.
System Attack on Cancer Cells
The existence of a PARP inhibitors have been
cancer cell can be a pre- approved for patients with breast
carious proposition. For or ovarian cancer who have
all its rowdy growth and inherited mutations in the BRCA
brash behavior, a tumor genes, as well as for some
cell may be struggling patients with recurrent ovarian,
to repair damage to its fallopian tube, or peritoneal can-
Both CDK4/6 inhibitors and PARP inhibitors
stimulate an immune system attack on DNA, an activity critical cer that responds to platinum-
cancer cells to its continued survival. based chemotherapy, and are
16 Paths of Progress 2020 Dana-Farber Cancer Institu teIan Krop, MD (left), Jean regrowth of the ovarian tumors –
Zhao, PhD (middle), and evidence that CD8+ T cells were
Shom Goel, MD, PhD
active participants in the assault
(right), in the lab.
on cancer cells. This finding,
coupled with further research,
mainly viewed as a re- provided convincing evidence
sponse to the die-off of that the immune response to
tumor cells triggered by PARP inhibitors is more than just
PARP inhibitors. Zhao a mop-up crew for dead cancer
and her colleagues cells but a partner in causing
wanted to determine if their death.
that was truly the case. Because BRCA1-deficient
To assist in this HGSOC tumors tend to wear a
effort, Liya Ding, PhD, thicker coat of PD-L1 proteins
a research fellow in after treatment with a PARP in-
Zhao’s lab, created hibitor, Zhao’s team theorized that
animal models of high- pairing the drugs with checkpoint
grade serous ovarian inhibitors would be even more
cancer (HGSOC), the effective. Experimental results
most common form bore that out: investigators found
of ovarian cancer, that mice treated with a PARP
in clinical trials for a range of that closely resembled HGSOC in inhibitor-checkpoint inhibitor
other cancers. humans. One set of models had a combination lived longer than
“In each of these cancers, the normal complement of the BRCA1 those treated with the PARP
consensus was that the drugs’ gene, the other lacked the gene. inhibitor alone.
effectiveness was due to the In the models without normal “These findings have important
direct killing of cancer cells,” BRCA1, researchers found that implications for the treatment
says Jean Zhao, PhD, of Dana- PARP inhibitors sparked an im- of ovarian cancer,” said Ursula
Farber and the Broad Institute, mune response that inundated Matulonis, MD, director of Gyne-
who led some of the recent the tumors with T cells and other cologic Oncology in the Susan
research into PARP inhibitors. immune system agents. “We F. Smith Center for Women’s
“We’ve shown that in the case of then asked whether the immune Cancers at Dana-Farber and a
ovarian cancer, another factor is response was meaningful. That co-leader of the research. “When
at play – the effects of the drugs is, does it actively contribute to used in conjunction with other
on the interaction of tumor cells inhibiting tumor growth or is it agents such as PD-1 inhibitors,
with the immune system.” primarily a passive response PARP inhibitors can have en-
In recent years, it’s become to the death of tumor cells?” hanced anti-cancer activity, and
clear that the immune system Zhao remarks. we now know why. The findings
responds to DNA damage in tumor In a series of experiments, add new impetus to clinical trials
cells by dispatching powerful they demonstrated that it is testing this combination.”
agents, including T cells and inter- overwhelmingly the former. In Many researchers believe
feron (proteins that intensify the one, they disabled T cells known that PARP inhibitors and CDK4/6
immune response) to the site of the as CD8+ T cells – which directly inhibitors are not the only agents
tumor. This immunological show attack tumor cells – after the to have a pleasant immunologi-
of force was thought to pose little animals had been treated with a cal surprise. Future studies will
threat to the tumor cells; it was PARP inhibitor. The result was a reveal if there are others.
www.dana-farber.org 17Shapeshifters 18 Paths of Progress 2020 Dana-Farber Cancer Institu te
in the Brain
New single-cell technologies
are revealing how aggressive
brain tumors evade treatment
BY NICOLE DAVIS
Glioblastoma is the worst of the worst. A form of and adult tumors. They uncovered some surprising
brain cancer that affects adults and children, it is similarities among the cells that drive these cancers,
both aggressive and difficult to treat. Tragically, most insights that could help spur new drugs aimed at
patients die within two years of diagnosis. But new glioblastoma.
research is cracking open the biology of the disease, “We’ve kind of come full circle in how we think
helping explain the tumor’s tenacity even when faced about adult and pediatric glioblastoma,” said Mari-
with targeted therapies. And those insights are at last ella Filbin, a lead author of the recent paper, which
giving scientists a critical toehold in the hunt for new, appeared in Cell, and a pediatric neuro-oncologist
more effective glioblastoma treatments. at Dana-Farber/Boston Children’s Cancer and Blood
In a study published last summer, a team from Disorders Center. “Up until about a decade ago,
Dana-Farber, Boston Children’s Hospital, and other we thought they were essentially the same, so we
leading research organizations used single-cell tech- treated them that way. But more recently, studies of
niques, which can examine the genetic information the tumors’ genomes revealed distinct genetic muta-
within individual cells, one at a time. The researchers tions – and that got us thinking that glioblastoma in
scrutinized more than 23,000 cells from both pediatric children is quite different than in adults.”
www.dana-farber.org 19Now, Filbin and her colleagues only a limited amount of surgery kids have such poor survival rates,”
are finding that the two cancers and radiation. It is also separated said Filbin. “We need to do better
may actually be more alike than from the bloodstream by a special and we need to do something dif-
not. They determined that the structure, the blood-brain barrier, ferent to understand that disease.”
cells that drive both adult and pe- which restricts the flow of drugs So she and her colleagues har-
diatric glioblastoma exist in four and other chemicals to brain nessed single-cell RNA sequenc-
distinct states, which are defined tissue, further complicating ing to examine nearly 2,500 cells
by the constellation of genes that treatment. from six DIPG patients. In a paper
are switched on or off – a kind Yet glioblastoma also has other published in Science in 2018, they
of molecular signature. These tricks up its sleeve. The tumor revealed that the majority of tumor
signatures closely resemble becomes interwoven into the cells are developmentally stuck –
those seen in the assortment of fabric of the brain, mingling with instead of growing up and becom-
normal cell types that make up normal structures and making ing more specialized, as normal
the developing brain. Importantly, itself inseparable from them. cells do, DIPG cells are trapped in
Filbin and her team revealed that “It’s actually like trying to an immature, stem-cell like state.
these driver cells are not static remove a virus with surgery,” said Filbin and her team also noticed
and can readily switch from one Keith Ligon, one of Filbin’s col- something else. Prior to any treat-
state to another, like a game of laborators and a neuropathologist ment, a small fraction of tumor
whack-a-mole. That discovery at Dana-Farber/Boston Children’s. cells can overcome this develop-
helps explain a sobering clinical Although Filbin understood this mental roadblock. They simply
reality: why existing, single-target dismal picture, she initially set out grow up or “differentiate”– and,
drugs for glioblastoma fail to curb to study a different cancer, a rare at the same time, lose their tumor-
the cancer’s growth. brain tumor called diffuse intrin- forming potential.
sic pontine glioma (DIPG), which “That is super exciting,” said
Opening Brain Cancer’s affects mostly young children and, Filbin. “We now have the first evi-
Bag of Tricks sadly, also has a grim prognosis. dence that a pediatric brain cancer
Like other forms of brain She was struck by the power of can differentiate on its own.”
cancer, glioblastoma is alarming new single-cell technologies, spe- She and her colleagues are
because of where it originates. cifically single-cell RNA sequenc- now exploring whether they can
As the epicenter of the mind ing, which provides a cell-by-cell exploit this capability therapeuti-
and body, the brain can endure snapshot of which genes are cally. Can a drug be identified that
active and which are not – the so- coaxes more tumor cells to dif-
called “transcriptome.” That view ferentiate, thereby rendering the
goes beyond what can be gleaned cancer harmless? This concept,
simply by looking at the cells’ known as differentiation therapy,
DNA, which only reveals which has been around for decades in
genes are missing or broken, not pediatric oncology and currently
how those changes impact cell forms the basis for treating a form
function. Because these tech- of pediatric leukemia as well as
niques are painstakingly applied another pediatric tumor called
to individual cells, they can reveal neuroblastoma.
subtle differences within a tumor
that may be missed by cruder, A Cell-By-Cell View
bulk profiling methods. of Glioblastoma
“DIPG was the very first cancer Filbin was so impressed with
Mariella Filbin, MD, PhD I wanted to look at because these the idea of differentiation therapy
20 Paths of Progress 2020 Dana-Farber Cancer Institu tefor pediatric brain cancers, she
wondered if it might apply to
other aggressive forms, like
glioblastoma. Her colleagues at
Massachusetts General Hospital
were already using single-cell
techniques to study adult forms of
the disease, so the researchers
banded together to conduct
a broader analysis of pediatric
as well as adult tumors. They
examined tumors from 20 adult
and eight pediatric patients.
Prior to the advent of single-cell
methods, scientists delved into Keith Ligon, MD, PhD, and Kin-Hoe Chow, associate director of the Center for
the molecular makeup of patients’ Patient Derived Models.
tumors using a bundled approach.
They would isolate a chunk of growth is fueled by four distinct explain why existing single-target
tumor tissue, grind it up, and per- cell types or “states,” which exist therapies fail to curtail glioblas-
form experiments on that cellular at varying degrees in all glioblas- toma growth.
“soup” – effectively averaging toma patients, both children and Unfortunately, the data do not
across all of the cells present adults. These states resemble give credence to differentiation
in the mix. And yet tumors don’t different cells normally found in therapy as an effective treat-
grow, spread, or die as an aver- the developing brain, including ment for glioblastoma, though,
age unit. They do so cell by cell. astrocytes and oligodendrocyte as Filbin’s earlier work indicates,
“A good analogy here is your progenitor cells, both types of it remains a promising approach
friendships,” said Ligon. “If you support cells called glia; neural for DIPG. Nevertheless, Filbin and
averaged all of your friends’ progenitors, which can give rise her team believe their findings
offer a roadmap for identifying
new glioblastoma therapies, and
“We now have the first evidence that a pediatric
they have launched early-stage
brain cancer can differentiate on its own.” research projects to pursue them.
“In every glioblastoma we
looked at, whether it was from a
– Mariella Filbin, MD, PhD kid or an adult, it had only those
four cell types, regardless of its
personalities, that won’t really tell to both neurons and glia; and genetic makeup,” said Filbin.
you anything about what each mesenchymal cells, which give “That gives us hope that if we
person is like.” rise to connective tissue. can find a way to block all four
With single-cell technologies, These glioblastoma cell states at the same time, we can kill
Filbin, Ligon, and their colleagues are highly plastic and can readily the tumor.”
were able to glimpse for the first shift from one to another. When Such a four-pronged attack
time a detailed picture of glioblas- Filbin and her colleagues injected would signify a groundbreaking
toma on a scale that matches just one of the four cell types into approach to glioblastoma treat-
its biology. mice, tumors formed that con- ment – one that could deliver
The team discovered that tumor tained all four types, helping to long awaited hope to patients.
www.dana-farber.org 21BRINGING
AI
TOWA R D BY ERIC BENDER
PERSONALIZED
CANCER CARE
Machine language technology brings
new power to study each individual’s
risks and best treatment options.
22 Paths of Progress 2020 Dana-Farber Cancer Institu teAsk your cellphone a question today, and it probably understands you
well enough to provide a fairly reasonable answer. That’s new. Ten years
ago, such ubiquitous and even expected speech recognition didn’t exist
anywhere on the planet. Now it’s on billions of mobile phones.
Much of your phone’s smarts are based on a rapidly advancing form
of artificial intelligence called machine learning, in which the computer
basically trains itself to find patterns within massive amounts of data.
Machine learning technologies are being applied in many fields, and
we’re just starting to see the impact they may have in medical research.
www.dana-farber.org 23Kenneth Kehl, MD, MPH, ( left) and Researchers at Dana-Farber But there’s a chokepoint for
Deborah Schrag, MD, MPH, (right) are bringing machine language research that taps into this
chief of Dana-Farber’s Division of
technology to many tough puzzles resource: It’s surprisingly difficult
Population Sciences.
in cancer. One pioneering project to capture how well patients are
is gathering information on treat- responding to treatment by ana-
ment outcomes in lung cancer, lyzing routine clinical records.
and a second one aims to better “As straightforward as one
identify people who are at most might expect that process to be,
risk to develop pancreatic cancer. it can be a substantial challenge,”
says Dana-Farber oncologist
Understanding Outcomes Kenneth Kehl, MD, MPH. He
in Lung Cancer explains that information about
Dana-Farber conducts a the patient outcomes shown in
genomic analysis on tumors from a CT scan, for example, may be
patients who give their consent. routinely recorded only in the
That genomic information can be unstructured text of a radiologist’s
essential to best understand an report. Tracking these outcomes
individual cancer and, in many requires trained staff to read and
instances, can help guide how annotate such records, which
to treat it. This genomic treasure can be slow and expensive.
trove can be combined with a Kehl and his colleagues turned
wealth of other patient informa- to machine-learning tools to auto-
tion, such as data from imaging, mate this painstaking process,
to offer an enormously valuable in a project funded by the National
resource for cancer scientists. Cancer Institute, the Claude
24 Paths of Progress 2020 Dana-Farber Cancer Institu teKehl points out. Treatment also labeling clinical data developed
has become more complex in by Schrag and her associates.
recent years with a flood of ap- The framework aims to ensure the
proved therapies to either target creation of gold-standard data
specific genetic mutations or on which all experts agree – and
to unleash the immune system in this case, it was applied to
against the cancer. annotating the outcomes that are
The Dana-Farber team began occurring in the CT scans.
by gathering more than 14,000 The researchers then applied
unstructured text reports on ra- a machine-language-based
diology images for 1,112 patients natural language processing
with lung cancer. Their next task approach that is designed to
entailed a large amount of human classify documents. “Just like
drudgery: building a database one can train AI algorithms to
of outcomes to help train the identify cats and dogs in pictures,
machine learning software, by one can train algorithms to look
manually labeling these unstruc- at text and identify, for example,
tured text reports. is the writer expressing positive
“Labeling is a fundamental or negative emotions about the
prerequisite for machine learn- subject?” Kehl says. “We used
ing – we have to teach machines one of these document classifica-
Dauphin Philanthropic Research from a high-quality curriculum tion techniques to do the same
Fund, and the Simeon J. Fortin if we want to get output we can thing. In our case, the model can
Foundation. The researchers trust to inform clinical decisions,” read the text of, say, a CT scan of
reported successful results for the says medical oncologist Deborah the lungs, and report out to us: Is
effort in a JAMA Oncology paper Schrag, MD, MPH, chief of Dana- cancer being described on this
in 2019. Their “natural language Farber’s Division of Population scan? If it is, is the cancer getting
processing” software performed Sciences and senior author on better or worse? And what areas
very strongly at interpreting the paper. “And labeling data is of the body are involved?”
unstructured textual records – unbelievably tedious.” The researchers demonstrated
matching up well against human Although machine language their software can generate out-
experts and delivering results projects often perform this initial come descriptions that are similar
exponentially faster. human labeling of data in ways to the descriptions generated by
The project focused on lung unique to each project, the people, and can do so dramati-
cancer, which is both very com- Dana-Farber team was careful to cally faster. Human curators took
mon and very difficult to treat, employ a standard framework for about 20 minutes to annotate a
single imaging report. In half that
“Labeling is a fundamental prerequisite for ma- time, Kehl and his colleagues esti-
mate, the computer models could
chine learning – we have to teach machines from annotate 30,000 imaging reports in
the study.
a high-quality curriculum if we want to get output Next, the text-processing soft-
ware examined reports for 1,294
we can trust to inform clinical decisions,” patients whose records had not
been manually reviewed. Investi-
– Deborah Schrag, MD, MPH gators confirmed that the soft-
www.dana-farber.org 25ware’s outcome measurements
in this group predicted survival
about as well as the human as-
sessments of outcomes among
the patients whose CT records
were manually reviewed.
The team is now working to
demonstrate that the patient
outcomes gathered by software
do indeed reflect known associa-
tions between tumor genomic
features and outcomes in lung
cancer, says Kehl. Once that’s
done, he, Schrag, and their
coworkers will start to ask new
research questions about con-
nections between treatments
and outcomes. The researchers
also will consider ways to incor-
porate such models into clinical
care delivery, such as finding
best ways to manage symptoms.
And they plan to check out how
well the models perform with
other types of cancer.
“Moving some of this AI work
into the clinic is important and
complex and challenging,” Kehl
says. “But it’s an important direc-
tion to take. It’s where the field
will have to go.”
Chris Sander, PhD, director of the cBio Center in Dana-Farber’s department of
Who Gets Pancreatic Cancer? Data Sciences.
When pancreatic cancer is
detected before it spreads, 37% The disease often can be to be practical for the population
of patients survive five years. detected at an early stage by at large.
Unfortunately, that’s the best- imaging with CT, MRI, or endo- Researchers know that pan-
case scenario. The survival rate scopic ultrasound. Currently, creatic cancer also is linked to
plummets to 10% if the tumor such screening is performed other factors including obesity,
is found at a later stage, which only for a very small group of smoking history, alcohol history,
happens in about 90% of cases. people thought to be at high risk and late-onset diabetes with
That’s one main reason that of the disease, either through weight loss and age. But there
pancreatic cancer is expected to family history or the presence of are no guidelines for integrat-
become the second-most-deadly certain worrisome genetic muta- ing all these factors to provide
type of cancer in the United tions. But pancreatic cancer is sufficiently reliable predictions
States by 2030. far too rare for such procedures of disease risk to allow effective
26 Paths of Progress 2020 Dana-Farber Cancer Institu tescreening to catch the cancer as
“We take a snapshot of a personal’s clinical
early as possible.
Producing such guidelines records, and starting with this raw data, we
through machine learning is the
goal of a project co-headed by challenge the artificial intelligence engine to
computational biologist Chris
Sander, PhD, director of the cBio learn, ‘What’s the probability that this person will
Center in Dana-Farber’s depart-
ment of Data Sciences, and
get pancreatic cancer in the next few years?’”
MIT computer scientist Regina
Barzilay, an expert on machine – Chris Sander, PhD
learning in medicine. Medical on-
cologist Brian Wolpin, MD, MPH,
and radiology physician-scientist data, we challenge the artificial Sander notes. “But if you want
Michael Rosenthal, MD, PhD, intelligence engine to learn, to apply the risk assessment AI
of Dana-Farber; epidemiologist ‘What’s the probability that this tool in clinical practice, then your
Peter Kraft of the Harvard T. H. person will get pancreatic cancer accuracy has to be very high to
Chan School of Public Health; and in the next few years?’” minimize the chance of unneces-
disease system biologist Søren Within their stockpiles of sary treatment.”
Brunak, PhD, of the University of clinical data, the team will look Truly effective screening
Copenhagen are collaborating at unstructured doctor notes programs also will demand more
on the effort, which is funded by (extracted with natural-language effective screening techniques.
Stand Up to Cancer. processing techniques similar to Hundreds of labs around the
Their work has begun with a those in the lung cancer proj- world are studying new methods
highly informative dataset that ect above), disease codes and of imaging or blood analyses for
includes complete clinical records treatment codes, blood tests, and early detection of solid tumors
for about 2.5 million patients in the images. “So far, we have the first such as pancreatic cancers.
Danish National Patient Registry, results from the disease codes, “There’s huge interest in that
about 20,000 of whom have had and we’re getting pretty good research,” Sander says. If better
pancreatic cancer, Sander says. results already,” Sander says. guidelines can be combined with
To meet stringent Danish privacy The two-year project aims to better screening, he and his
requirements, researchers actu- produce sufficiently accurate colleagues hope for real progress
ally must make repeated trips to risk guidelines for a clinical trial against this fearsome form
Copenhagen for access to the screening for early signs of cancer.
Danish computing resources. The of cancer. Scientists also hope “Our clinicians at Dana-Farber
project also will extract risk pro- their algorithms will shed light do a lot of work on curing cancer
files from the Henry Ford Health on the roles various risk factors when it’s very advanced, which
System in Detroit and Partners have in predicting (and maybe is where the suffering is and
HealthCare in Boston. even causing) the disease and where we really need to beat the
In building machine-language how these could be used in cancer,” he adds. “But it’s also
algorithms, “we’re not going in prevention programs. important to try to catch cancer
with preconceived notions of To enter standard clinical at the early stages, avoiding all
what are the deciding factors for care, the guidelines will have to the suffering along the way and
risk,” Sander says. “We take a deliver very high accuracy. “You bringing down the total cost of
snapshot of a personal’s clinical can have less than 100 percent treatment, and that’s one of our
records, and starting with this raw accuracy for a clinical trial,” top priorities.”
www.dana-farber.org 27You can also read
