TheoryLab American Cancer Society

Inflammatory breast cancer (IBC) is rare and accounts for only 1% to 5% of all breast cancers, but it is considered an aggressive cancer because it grows quickly and is more likely to come back after treatment than other types of breast cancer. It causes symptoms of breast inflammation like swelling and redness, which is caused by cancer cells blocking lymph vessels in the skin causing the breast to look "inflamed."

Gayathri R. Devi, PhD, is a two-time American Cancer Society grantee who recently received a Mission Boost Grant to “boost” her inflammatory breast cancer research and move it closer to patients.

Dr. Devi joined the podcast to talk about risk factors for IBC, how it’s different from other breast cancer types, and recent advances in her lab with promising clinical implications.

Dr. Devi is Program Director for the Duke Consortium for Inflammatory Breast Cancer, Associate Professor of Surgery and Pathology at Duke School of Medicine, and the Director of the Duke North Carolina Central University bridge office as part of the Duke School of Medicine Clinical and Translational Sciences Institute.

3:18 – The symptoms and signs of inflammatory breast cancer (IBC)

6:34 – How inflammatory breast cancer differs from other, more common breast cancers

9:36 – Risk factors for inflammatory breast cancer

14:22 –Instead of a single tumor mass, IBC patients have small groups of tumor cells called emboli found in the breast, skin and lymph nodes around the breast tissue. What are emboli? How do they form?

16:00 – Why do emboli form in this way?

18:51 – What makes these emboli resistant to treatment and able to spread?

21:43 – On her ACS-funded research, which focuses on the environment in which the IBC emboli form, in the breast. Why is the breast environment so important?

28:35 – Adaptive stress response

31:15 – “I’ll give you an example here and talk a little about our research findings that are clinically relevant.”

38:25 – How do we target inflammatory breast cancer therapeutically?

40:47 – The 3M approach: Models, Mechanisms, and Measures

45:30 – If she could wave a magic anti-IBC wand, where would we be in 5 years?

48:27 – The impact that ACS funding has had on this area of research

49:54 – “Another very important distinction about ACS…”

51:47 – How inflammatory breast cancer recently affected her family

The first few minutes of this conversation is for a lay audience, as Elham Azizi, PhD, and Charly Good, PhD, explained how they’re investigating what causes cancer to grow and spread and how to improve immunotherapy.

Then the discussion moved toward a scientific audience, as Drs. Azizi and Good shared recent findings and asked probing questions about future directions and opportunities in cancer research.

Elham Azizi, PhD, is a former American Cancer Society postdoctoral fellow who is now an Assistant Professor of Biomedical Engineering at Columbia University. She joined the podcast to share findings from her recent publication, “Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy” (https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01471-6#secsectitle0020).

Charly Good, PhD, is an American Cancer Society postdoctoral fellow in the lab of Shelley Berger, PhD, at the University of Pennsylvania. She recently published research in Cell on “An NK-like CAR T cell transition in CAR T cell dysfunction” (https://www.cell.com/cell/fulltext/S0092-8674(21)01331-3).

FOR A GENERAL AUDIENCE

1:25 – Dr. Azizi explains how her lab uses machine learning techniques and other cutting-edge technologies to understand what’s happening in the tumor microenvironment

2:47 – Dr. Good describes the focus of her research—using the patient’s own immune system to attack cancer

FOR A SCIENTIFIC AUDIENCE

4:19 – Dr. Good describes takeaways from her recent publication on “An NK-like CAR T cell transition in CAR T cell dysfunction” (https://www.cell.com/cell/fulltext/S0092-8674(21)01331-3)

7:25 – Dr. Azizi reacts to the paper…

8:51 – …and asks why some patients didn’t see an increase in NK receptor expression

12:22 – Dr. Azizi shares findings from her paper, “Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy” (https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01471-6#secsectitle0020)

17:40 – Dr. Good asks: “Was it at all surprising to you when you first realized that the exhausted population was specific to the responders pre-infusion?”

22:10 – What’s next in machine learning?

26:03 – On the impact of ACS funding on their research

30:26– Why it’s an exciting time for cancer research

Corinne Leach, PhD, MPH, MS, who leads cancer survivorship research at the American Cancer Society, joined the podcast to discuss her recent publication on the rise of mental health distress during the COVID-19 pandemic.

Using data from the American Cancer Society Cancer Prevention Study-3 (CPS-3) cohort, Dr. Leach and collaborators “identified factors associated with increased depression and anxiety during the pandemic, including sociodemographic characteristics, stressors, and comorbid conditions associated with increased risk for poor COVID-19 outcomes.”* They also presented findings related to financial stressors and looked at long-term implications.

For resources and information to help you cope during and after cancer treatment, please visit: https://www.cancer.org/treatment/survivorship-during-and-after-treatment.html

Dr. Leach is Senior Principal Scientist of Behavioral Research in the Population Sciences group at the American Cancer Society. She serves as the Principal Investigator of the American Cancer Society (ACS) survivorship cohorts, including the Studies of Cancer Survivors and the Cancer Survivor Transition Study.

3:13 –Pandemic-related stressors that have been associated with greater levels of anxiety and depression

8:09 – Her recent study on how our mental and physical health prior to the pandemic factored into our ability to deal with the psychological stress of the pandemic

10:57 – On long-term implications for mental health

12:45 – A snapshot of what cancer survivorship looks like in the United States

15:09 – On similarities between cancer survivors and participants her your study whose stressors were associated with anxiety and depression

17:25 – On post-treatment programs for cancer survivors

21:51 – Helpful ways to deal with significant life stressors

* http://pressroom.cancer.org/StressorsPandemicPredictors

People going through cancer treatment sometimes have cognitive changes such as trouble remembering, paying attention, or thinking clearly.

Drs. Judith Carroll and Kathleen Van Dyk are clinician scientists who help patients with cancer-related cognitive impairment and conduct research into what causes it, how to identify patients at risk for it, and how to reverse its effects.

Judith Carroll, PhD, is Associate Professor in the Department of Psychiatry and Biobehavioral Science at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, and she’s the term Endowed Chair of the George F. Solomon Professorship in Psychobiology at UCLA. She’s also a Member of the Cousins Center for Psychoneuroimmunology. She received American Cancer Society funding to support her research on “Biobehavioral Vulnerability to Accelerated Aging In Breast Cancer Survivors” from 2016-2020.

Kathleen Van Dyk, PhD, is Assistant Professor in the Department of Psychiatry and Biobehavioral Science at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, and she’s a practicing neuropsychologist. She was an American Cancer Society postdoctoral fellow, studying “Cognitive Decline in Breast Cancer Survivors,” from 2017-2019.

INCIDENCE AND NATURE OF THE PROBLEM
2:09 – What is “cancer-related cognitive impairment?” Is it the same as “chemo brain?”

3:12 – How common is it?

4:41 – What kind of symptoms does it produce?

CONTRIBUTING FACTORS AND MECHANISMS
6:54 – Is cancer-related cognitive impairment a side effect of cancer? Is it caused by certain treatments?

12:11 – How has COVID impacted cognitive impairment among breast cancer survivors?

14:22 – On the biology of aging and how cancer could accelerate the aging process

TREATMENT
17:48 – Is cancer-related cognitive impairment reversible?

22:04 – On the exciting potential of sleep interventions

23:54 – Understanding the effects of endocrine therapies on brain function

CLOSING THOUGHTS

25:42 – How ACS funding has impacted their career and research

29:40 – A message they’d like to share with cancer patients, survivors, and caregivers who are concerned about cancer-related cognitive impairment

In this episode of the TheoryLab podcast, two American Cancer Society grantees discussed key takeaways from their recent publications.

In the first part of the conversation, which is intended for a lay audience, Dr. Joshua Andersen and Dr. Bhuminder Singh talked about targeted therapies, treatment side effects, and drug resistance.

Then they moved into a more technical discussion of their recent papers.

Dr. Andersen recently published findings showing that “TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.”
https://doi.org/10.1038/s41467-021-25622-3

Dr. Singh published a study recently showing that “Induction of apically mistrafficked epiregulin disrupts epithelial polarity via aberrant EGFR signaling.”
https://doi.org/10.1242/jcs.255927

Joshua L. Andersen, PhD, is Associate Professor of Biochemistry at Brigham Young University. He is a two-time American Cancer Society grantee.

Bhuminder Singh, PhD, is Assistant Professor of Medicine and Cell and Developmental Biology at Vanderbilt University Medical Center, and he is also a two-time American Cancer Society grantee.

1:25 – Dr. Andersen explains why his lab is focused on improving targeted therapies

2:31 – Dr. Singh describes how his research is focused on addressing drug resistance in colorectal cancer

4:28 – Dr. Andersen dives into his lab’s new Nature Communications paper on a new cancer driver—"it’s been probably the most rewarding project that I’ve been a part of in my career”

8:11 – Dr. Singh asks a few questions about the paper: “Are there any mutations in TNK1 in human cancer?”

10:01 – What ubiquitinated proteins was it binding to?

11:44 – Is TNK1 itself ubiquitinated in certain conditions?

12:49 – Dr. Singh explains takeaways from his paper, “Induction of apically mistrafficked epiregulin disrupts epithelial polarity via aberrant EGFR signaling”

19:16 – Follow-up questions from Dr. Andersen: “How could the mistrafficking of a single ligand affect its localization so dramatically?”

22:04 – “That has to send a signal then to start trafficking the intracellular EGFR out to the apical side of the cell, right?”

27:49 – “As someone who hasn’t really thought about cell polarity very much inside a solid tumor, what would be the effects of mistrafficking in terms of the architecture of a solid tumor?”

31:18 – The impact of American Cancer Society funding on their research

When a cancer patient has a serious diagnosis, clinicians and families can struggle with how patients experience hope.

Three distinguished palliative care physicians and researchers joined the podcast for a conversation about their recent paper in JAMA titled, “Holding Hope for Patients with Serious Illness” (https://jamanetwork.com/journals/jama/article-abstract/2784454).

Drs. Abby Rosenberg, Robert Arnold, and Yael Schenker shared their own experiences treating seriously ill patients and talked about how we can navigate the tension between appreciating the potential therapeutic benefit of hope and being concerned about perceived unrealistic hopes:

“Rather than being concerned that hope is either so fragile that it can be lost, or so powerful that it can overwhelm decision making, clinicians should remember that hope is protective, if not necessary, for managing serious illness. Holding complex, flexible, and diverse hopes enables patients to believe in the unlikely while simultaneously accepting the inevitable. The role of clinicians is to support both.”

Abby Rosenberg, MD, MS, MA, is a pediatric oncologist and palliative care physician and researcher at the University of Washington, where she directs the pediatrics component of the Cambia Palliative Care Center, and Seattle Children’s Research Institute, where she directs the Palliative Care and Resilience Lab. She has an American Cancer Society Research Scholar Grant to study “Resilience Outcomes Among Adolescents and Young Adults with Advanced Cancer.”

Robert M. Arnold, MD, is a palliative care physician, Distinguished Professor of Medicine, and Chief of the Palliative Care Section at the University of Pittsburgh. He previously served as a member of the American Cancer Society’s palliative care peer review committee.

Yael Schenker, MD, MAS, is a palliative care physician, Professor of Medicine, and Director of the Palliative Research Center (PaRC) at the University of Pittsburgh. She is a past recipient of American Cancer Society research funding, which supported her study of “Primary Palliative Care for Patients with Advanced Hematologic Malignancies.”

3:27 - The therapeutic benefit of hope and why it’s helpful to patients and caregivers

5:12 – Why clinicians sometimes feel the need to “correct” a patient’s hope

8:56 – How physicians can address the tension of appreciating the potential therapeutic value of hope but being concerned about perceived unrealistic hopes

10:50 – On how physicians can help patients diversify and increase their hopes

6:24 – How they became interested in this topic and decided to explore this topic in a broader way

17:35 – Advice they would share with someone in medical school who might someday treat patients with a poor prognosis

19:03 – A message for caregivers of a patient with a terminal illness