summer 2018 pancreas center news -...
TRANSCRIPT
In This Issue
FROM THE DIRECTOR
2 Moving Toward a Breakthrough
RESEARCH PROFILES
3 BRCA Research Opens Window on Precision Pancreatic Cancer Medicine
4 Opening New Prevention and Treatment Pathways
STAFF PROFILES
5 Connecting With Patients: New NP Brings Experience, Expertise
6 Honoring Pancreas Center Nurse Elizabeth Dito
DONOR PROFILE
7 Lynne Deegan-McGraw: Supporting Better Options for Pancreatic Cancer Patients
BRCA Research Opens Window on Precision Pancreatic Cancer MedicineIn 2011, when gastrointestinal oncologist
Julia Carnevale, MD, began her training at UCSF,
advanced melanoma was a universally grim diagnosis.
She recalls rotating through a cancer clinic and
hearing oncologist Adil Daud, MD, speaking with
a patient about a trial of a new immunotherapy
drug, a PD-1 checkpoint inhibitor.
SUMMER 2018
Pancreas Center News
(Continued on Page 3)
2
Moving Toward a Breakthrough2018 marks the UCSF Pancreas Center’s fifth anniversary.
Thanks to the hard work of many people here and around
the world, pancreatic cancer survival rates have inched up,
but we have not yet seen the breakthroughs that we’ve
seen with many other cancers. That painful fact pushes
our determined team of clinicians and researchers to find
new approaches that will offer hope for our patients
and their families.
Increasingly, our efforts include reaching out to
researchers working on other cancers and other diseases.
We are spearheading the creation of a program that
leverages the University of California’s BRAID program.
BRAID aims to accelerate research and improve health
through collaboration, sharing resources, and infrastructure
development across UC campuses. We are traveling
around the world and learning new ways to speed the
testing of novel therapeutic agents. We continue our work
on early screening in collaboration with the UCSF Diabetes
Center and the Kaiser Foundation Research Institute.
Many of these efforts now focus on understanding
the diversity of this disease so we can personalize risk
assessment, early detection, and treatment. This issue
highlights two exciting avenues of research in that area.
A BRCA gene mutation now appears to be a factor
in about 10 percent of pancreatic cancer patients. Alan
Ashworth and Julia Carnevale at the UCSF Center for
BRCA Research are leading some of the most promising
work aimed at screening for the mutation and devising
strategies to defeat BRCA-driven cancers. On another front,
Valerie Weaver now pairs her groundbreaking work on the
interaction between tumors and their microenvironments
– including understanding genetic mutations that cause
tumors to produce fibrotic tissue linked with more
aggressive forms of pancreatic cancer – with imaging
techniques to capture these risks in their more treatable
early stages.
Finally, because the best cancer care goes far beyond
the mechanics of diagnosis and treatment, we highlight our
new nurse practitioner, Patricia Zendejas, and our longtime
nurse Elizabeth Dito, who has moved on to the Cancer
Center’s Symptom Management Service after more than 16
years of outstanding work here. Their innovative expertise
in symptom management and patient education, vigorous
patient advocacy, and humane help for patients and families
navigating the challenges of this disease are central to the
type of care we pride ourselves on delivering.
Please know: Driven by the statistics – and more
importantly, by our interactions with our patients and their
families – we continue pressing onward as hard as humanly
possible for the breakthrough we all believe is right around
the corner.
Margaret Tempero, MD Director, UCSF Pancreas Center Rombauer Family Distinguished Professor in Pancreas Cancer Clinical and Translational Science
Margaret Tempero, MD
FROM THE DIRECTOR
3
BRCA Research (Continued)
“Fast forward to today, and the landscape for melanoma
patients has completely changed for the better,” she says.
“You never know what opportunities a trial might open up.”
That moment – and her personal
experience with pancreatic cancer –
helps the clinician-researcher believe that
technological advances could already be
informing a clinical trial that will someday,
says Carnevale, “stop a pancreas tumor
in its tracks.”
Understanding BRCAIn her research role, Carnevale works
with Alan Ashworth, PhD, FRS, president
of the UCSF Helen Diller Family
Comprehensive Cancer Center and
founder of the UCSF Center for BRCA
Research – one of only two such centers
in the United States. Among its efforts,
the lab is increasing understanding of how
mutations in the BRCA gene contribute
to pancreatic cancer and can be used to
improve therapy.
“Recent work indicates that perhaps
1 in 10 pancreatic cancer patients –
maybe more – have a BRCA2 mutation
or a mutation in a the same cellular
pathway,” says Ashworth. By drawing on
PARP inhibitor (PARPi) therapies already
FDA-approved for BRCA-driven breast
and ovarian cancers, his team hopes
to discover a new precision medicine
approach for pancreatic cancer patients
with the mutation.
Using a technique developed at UCSF,
the lab has completed the first “CRISPRi”
screens in BRCA2 mutant cells. The
screens help researchers understand
why some patients experience sustained
clinical responses when treated with PARPi
while tumors in others fail to respond,
with drug resistance often occurring in
advanced disease.
“We hope to find something to add to
the PARPi to make the response more
durable,” Ashworth says.
Carnevale also is working on a
collaborative project to develop
a new CRISPR technique
that will enhance the immune
system’s ability to kill cancer
cells in the pancreas.
Laying the Groundwork for Clinical TrialsAs that work advances,
Ashworth, Carnevale and their
colleagues have been building
a program to have every UCSF
cancer patient complete a
simple genetic test to determine whether
they carry a mutation in BRCA1, BRCA2,
or related genes. The more participation,
the more likely the team can identify
patients who are a good fit for promising
pancreatic cancer trials – just as Daud was
doing with his melanoma patients seven
years ago.
“Synergies between disease-specific
groups are exactly what we wanted to see
when we established the BRCA Center,”
says Ashworth, “and Julia is the perfect
person to bridge this work into the
clinical world.”
To learn more, visit brca.ucsf.edu.
RESEARCH PROFILE
Julia Carnevale, MD
BRCA mutant pancreatic cancer cells
“ You never know what
opportunities a trial
might open up.
”Julia Carnevale, MD
4
RESEARCH PROFILE
Opening New Prevention and Treatment PathwaysValerie Weaver, PhD, is a pioneer in demonstrating that
the interaction between tumors and their surrounding
microenvironments, or stroma, can create tense, highly fibrotic
tissue that confounds treatment attempts and enables cancer cells
to thrive. This is a particularly relevant finding for pancreatic cancer,
which displays more of this fibrotic tissue than any other cancer.
Driven by evidence that indicates cancer
cells are “addicted to tension,” Weaver –
director of the Center for Bioengineering
and Tissue Regeneration in the UCSF
Division of General Surgery – is now trying
to define the precise regulators of that
tension and create new opportunities for
early detection, therapy, and prevention.
Schwarzenegger TumorsIn a 2016 article in the journal Nature Cell
Biology, Weaver and her team provided the
first evidence linking tumor aggressiveness
and patient survival rates in pancreatic
ductal carcinoma (PDAC) to underlying
genetic mutations that cause tumors
to stiffen and produce fibrotic tissue
around them.
In brief, the tissue exerts physical forces
on the tumor it surrounds, the tumor
responds with its own physical forces,
and the intensity of that tug-of-war has
a major impact on how aggressive the
cancer becomes. Moreover, Weaver’s 2016
article suggested that people with cancer-
causing gene mutations such as SMAD4
can wind up with what Weaver calls
“Schwarzenegger tumors.” The intense
back-and-forth between the tumor and
stroma wraps the tumor so tightly
in tissue that it can resist nearly any
known therapy.
Digging DeeperNow Weaver’s work is zeroing in on the
glycocalyx, a slimy coating on the outside
of cells associated with increased tension,
which creates an “immune desert” that
prevents the body from fighting cancer.
“Aggressive pancreatic tumors have a
profound glycocalyx,” says Weaver.
For such tumors, anti-fibrotic therapy
might provide temporary relief, but by the
time the cancer has been diagnosed, the
tumor has already reprogrammed itself
to ramp up the tension again and remain
highly resistant to therapy.
“If we can capture people in the
early stages of disease who have these
super-aggressive mutations, anti-fibrotic
approaches and other therapies that inhibit
the signaling that causes tension might be
more effective,” says Weaver. She is also
working with a Stanford University chemist
to develop “sponges” that could bind up
and degrade galectin – a protein that turns
on the mechanisms that create and stiffen
the glycocalyx.
Yet early detection is still the key, so
Weaver and UCSF radiologist Z. Jane
Wang, MD, are testing whether computed
tomography (CT) imaging can identify the
most aggressive tumors, ideally in early or
precancerous stages.
“My hope is that early detection will
enable us to pre-empt the tumor and
stroma from stiffening, or at least enable
us to stratify patients to better target
certain treatments, and in doing so, open
new ways to treat pancreatic and other
cancers,” Weaver says.
To learn more about the Weaver lab,
visit weaverlab.ucsf.edu.
“ The intense back-
and-forth between
the tumor and stroma
wraps the tumor so
tightly in tissue that it
can resist nearly any
known therapy.
”Valerie Weaver, PhD
Dr. Weaver is inducted into the American
Institute for Medical and Biological Engineering
5
New NP Brings Experience, Expertise When nurse practitioner (NP) Patricia Zendejas joined the
UCSF Pancreas Center in February 2018, she brought with
her a wealth of experience sure to benefit patients undergoing
the stresses of pancreatic cancer diagnosis and treatment.
Zendejas grew up in San Francisco,
speaking Spanish and English with her
Mexican-born parents. After graduating
from UC Santa Cruz in 1995, she moved
to New York and earned a master’s degree
in social work from Columbia University.
She then spent six years in New York as a
social worker, including during and after the
trauma of 9/11.
Nursing: Her True Calling“It was rewarding, but when I came back
to San Francisco, I thought nursing might
be my true calling,” she says. At the UCSF
School of Nursing, she earned her RN, a
master’s degree, and her credential as an
adult NP. After graduation in 2010, she
began her nursing career, ultimately serving
as a primary care NP at La Clínica de La
Raza in Oakland, Calif.
During that time, however, she kept in
touch with colleagues she had worked with
during a clinical rotation in gastrointestinal
(GI) oncology at the Stanford Cancer
Center – a time she remembers fondly.
“The relationship you develop with
a patient in that setting was so fulfilling
because you create such a deep, intimate
connection so quickly,” she says. When
the NP whom Zendejas had worked with
retired, she recommended that Zendejas
apply for the job.
She spent 4½ years at Stanford, until
UCSF called. Zendejas, who still lives in
San Francisco, felt it was a good time for
another transition. She arrived in February
and sees patients with all GI cancers but
with a special focus on pancreatic cancer.
As an NP, Zendejas’s primary role is to
help manage symptoms
and the side effects of
medication, but she
also serves as a bridge
between the oncologists
and the nurses, who
have impressed her with
their expertise. “We start
creating a relationship
with patients and families
from the very first visit and
follow patients very closely throughout their
care,” she says.
In addition, because Zendejas sees
patients independently during their
follow-up clinic visits, her presence frees
the oncologists to see more new patients.
Zendejas hopes in the months ahead,
she can use her bilingual, bicultural
background to attract more Spanish-
speaking patients to UCSF and engage
more of them in research – an area in which,
traditionally, they are underrepresented.
For the moment, however, she is thrilled
with her new position.
“I’ve been so impressed with the level
of attention patients receive from our entire
team,” she says.
“ The relationship you
develop with a patient
in that setting was so
fulfilling because you
create such a deep,
intimate connection
so quickly.
”Patricia Zendejas
Patricia Zendejas
STAFF PROFILE
6
STAFF PROFILE
Honoring Pancreas Center Nurse Elizabeth DitoElizabeth Dito has been the face of the UCSF Pancreas
Center for more than 16 years. In April 2018, she moved on
to become a core member of the UCSF Helen Diller Family
Comprehensive Cancer Center’s Symptom Management
Service. In her new role, Dito will continue to see pancreatic
cancer patients, but her daily presence will be missed.
We sat down with Elizabeth before she left and asked her
about her role at the Pancreas Center and her thoughts
looking back on her time with us.
“My primary focus over the last 16 years has been to
develop a relationship with each patient, from diagnosis
to treatment and beyond. Patients and families have our
nurses’ pager numbers and a direct line to our desks
because we know it gives them a sense of comfort and
helps us be their advocates and a liaison to their physicians.
“Over time, my role changed as I became more
attuned to the nuances of patients with this disease.
Subtle changes in pain, signs that something was brewing
such as an infection or mood changes – they would all
trigger something in me. I would bring the symptoms to
physicians who would follow through with treatment, and
ultimately I assumed a bigger role in managing symptoms,
whether they were from the disease or the treatment.
“After auditing a palliative care class and reviewing
research, I felt nurses needed more educational programs
on interdisciplinary palliative care – holistically managing
the physical, psychological, and spiritual symptoms
associated with undergoing treatment for a life-limiting
illness. After a formal needs evaluation and consultation
with Dr. Tempero and the Symptom Management Service,
we received philanthropic funding to develop the classes.
This is our third year, and with the help of our advisory
committee, we now offer nurses four courses each year.
“In my new role, I’m a symptom-management nurse
for cancer patients in various specialty clinics, part of an
interdisciplinary team that also includes a physician or
nurse practitioner, a social worker, and a chaplain. One
of my eventual goals is to develop nurse-led teaching
sessions for patients undergoing cancer treatment.
“One of the reasons I stayed at the Pancreas Center for
so long is that I really liked the people I worked with. From
early on, I built a trusting relationship with Dr. Tempero and
Andrew Ko, MD, who gave me freedom to practice within
my scope. And as the program grew, the same was true
for my relationship with my nursing colleagues and other
members of the care team. Without the mutual respect,
I wouldn’t have been able to provide the depth of care
to the patients. The UCSF Pancreas Center is filled with
people dedicated to learning more about this disease and
how to treat our patients and families with compassion
and respect.”
“ She elevated the standard of care
like you wouldn’t believe.
”Margaret Tempero, MD
7
DONOR PROFILE
Lynne Deegan-McGraw: Supporting Better Options for Pancreatic Cancer PatientsIn Fall 2004, after distinguished careers in the tech industry,
Lynne Deegan-McGraw and her husband, John, were
just beginning to enjoy their retirement in Sonoma Valley
when John’s health began to fail. After a long and painful
odyssey, he was diagnosed with pancreatic cancer. His
physician told them there likely was nothing they could
do except possibly apply for a clinical trial led by UCSF
Pancreas Center director Margaret Tempero, MD.
“From day one, Margaret was clearly an outstanding
clinician, but it was also her bedside manner, the way
she focused on John. Her empathy was incredible,” says
Deegan-McGraw. “We didn’t think he was going to make it to
Christmas, but she gave us both hope.”
Dr. Tempero immediately put John on a chemotherapy trial
and called the first night to see how he was doing. She made
housecalls to Sonoma Valley. The nurses too, says Deegan-
McGraw, were incredible. “We had their cell phone numbers,
and they kept me sane,” she says.
John lived another 15 months, three months past the clinical
trial’s end date. “He got a lot better for a while, and it’s my belief
that Margaret gave us an extra year,” says Deegan-McGraw.
Out of gratitude for the type of care she and her husband
received – and because she knows all too well that pancreas
cancer remains a devastating diagnosis with survival rates of
less than 10 percent – Deegan-McGraw supports the UCSF
Pancreas Center in two distinct ways.
First, she periodically provides gifts to support the center’s
diverse efforts. Second, she says, “I’m fortunate enough to
have an estate, and I have included a significant bequest to
UCSF for when I am no longer here.”
Her thinking is simple: Despite progress, late detection
means pancreas cancer still has a terrible prognosis for most.
“My husband was fit and healthy until it was too late,” she
says. “I hope a gift like mine can support a large and dedicated
team of researchers so we can better understand the risk
factors and get to early diagnoses.”
By raising awareness, she hopes that others – those who
have been touched by the disease and even those who haven’t
– will join her in this effort.
“ I hope a gift like mine can support a large and dedicated
team of researchers so we can better understand the risk
factors and get to early diagnoses.
”Lynne Deegan-McGraw
0906
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Pancreas Center News
Managing Editor: Susan Godstone
Writer: Andrew Schwartz
Design: Shirley Chambers
Photography: Steve Babuljak; Elisabeth Fall; Susan Merrell
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