TheoryLab

Two American Cancer Society grantees—one with a recent publication on the early mechanisms of lung cancer initiation, the other with a new study out on the development of melanoma resistance during the earliest phases of treatment—joined the podcast for a conversation about catching the problem early.

This conversation is geared for a scientific audience, until the last few minutes.

Sabrina Spencer, PhD, is Associate Professor of Biochemistry at University of Colorado, Boulder. She recently published a study in Nature Communications on “Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signaling:” https://www.nature.com/articles/s41467-021-21549-x?elqTrackId=2842c2f36cc243139afc4151f4f48ee6.

Xaralabos (Bob) Varelas, PhD, is Associate Professor of Biochemistry at Boston University School of Medicine. He recently published work in Proceedings of the National Academy of Sciences of the United States of America titled, “Aberrant epithelial polarity cues drive the development of precancerous airway lesions:” https://www.pnas.org/content/118/18/e2019282118.

1:08 – Dr. Varelas on his recent study, which offered insights into mechanisms that drive the onset of lung squamous cell carcinomas

4:20 – Dr. Spencer asks clarifying questions about how they disrupted the polarity…

5:08 – …and whether the Crumbs3 mutation occurs in patients or was a way to initiate the system

7:56 – A provocative question from Dr. Spencer: “would that mean that a precancerous lesion would be a candidate for treatment with some of these clinically approved drugs?”

9:25 – “Can you connect increased ERBB signaling to actual increased cell cycling?”

10:48 – Dr. Spencer talks about her interest in the origin of drug resistance in cancer and her recent paper, which focused on melanoma

20:15 – Dr. Varelas asks how broadly applicable these findings are to other cancers

22:10 – “Why do you think some of the cells escape? Is there an underlying difference in the cells to begin with? Or are some cells randomly taking on some kind of adaptive mechanism?”

28:11 – The impact of American Cancer Society funding on their research

When tumors grow within the body they press on surrounding tissues, building up pressure. Pancreatic cancer builds up more pressure than any other cancer.

Why is that? How do cancer cells adapt to this high-pressure environment or take advantage of it?

In the words of Liam Holt, PhD, “Normal cells and early-stage cancer cells stop growing when pressure builds up. In contrast, in advanced cancer, compression can change cellular behavior to drive migration of cancer cells to other organs or confer resistance to chemotherapy… By determining the fundamental biology of pressure adaptation, we may discover strategies to treat this currently untreatable disease.”

Liam Holt, PhD, is Associate Professor at the NYU School of Medicine.

1:50 – Why do pressure and compression matter for normal cells?

“From the earliest embryo through to astronauts, we can find really good examples of how cells are responding to their mechanical environment to make sure they do just the right thing.”

6:09 – What happens when a tumor starts to grow? How does that affect nearby normal cells?

11:08 – Why there is so much compressive stress inside pancreatic tumors

16:24 – If we gain a better understanding of how pressure impacts pancreatic cancer, could that help us prevent or treat cancer?

22:13 – How a high-pressure environment drives the diversity of cancer cells

26:19 – “You can usually tell if it’s a good idea because it seems super obvious”

29:06 – On an educational outreach initiative he co-founded called Science Sketches

https://www.sciencesketches.org/

33:48 – The impact American Cancer Society funding has had on his research

34:59 – A message he’d like to share with cancer patients, survivors, and caregivers

When tumors grow within the body they press on surrounding tissues, building up pressure. Pancreatic cancer builds up more pressure than any other cancer.

Why is that? How do cancer cells adapt to this high-pressure environment or take advantage of it?

In the words of Liam Holt, PhD, “Normal cells and early-stage cancer cells stop growing when pressure builds up. In contrast, in advanced cancer, compression can change cellular behavior to drive migration of cancer cells to other organs or confer resistance to chemotherapy… By determining the fundamental biology of pressure adaptation, we may discover strategies to treat this currently untreatable disease.”

Liam Holt, PhD, is Associate Professor at the NYU School of Medicine.

1:50 – Why do pressure and compression matter for normal cells?

“From the earliest embryo through to astronauts, we can find really good examples of how cells are responding to their mechanical environment to make sure they do just the right thing.”

6:09 – What happens when a tumor starts to grow? How does that affect nearby normal cells?

11:08 – Why there is so much compressive stress inside pancreatic tumors

16:24 – If we gain a better understanding of how pressure impacts pancreatic cancer, could that help us prevent or treat cancer?

22:13 – How a high-pressure environment drives the diversity of cancer cells

26:19 – “You can usually tell if it’s a good idea because it seems super obvious”

29:06 – On an educational outreach initiative he co-founded called Science Sketches

https://www.sciencesketches.org/

33:48 – The impact American Cancer Society funding has had on his research

34:59 – A message he’d like to share with cancer patients, survivors, and caregivers

In this episode, Gustavo Martinez, PhD, and Daniel Herranz, PhD, discussed their new cancer research publications. Dr. Martinez talked about his research into how T cells respond in the context of cancer, and Dr. Herrera explained his lab’s findings related to targeting cancer metabolism in leukemia.

Gustavo Martinez, PhD, is Assistant Professor at Rosalind Franklin University. He received American Cancer Society funding to support his research into T cell exhaustion and boosting our immune system’s response against cancer.

Daniel Herranz, PhD, is Assistant Professor of Pharmacology at Rutgers, The State University of New Jersey. His ACS-funded research focuses on T-cell acute lymphoblastic leukemia.

The first half of the conversation is more technical and is directed towards a scientific audience. The second part, starting at 17:27, is for all audiences.

1:38 – Dr. Martinez on the focus of his lab and takeaways from his recent publication in The Journal of Immunology titled, “Kdm6b Regulates the Generation of Effector CD8+ T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes:” https://www.jimmunol.org/content/early/2021/04/16/jimmunol.2001459

4:40 – What are some next steps? Are there downstream targets that could be activated?

7:54 – Dr. Herranz talks about why he’s interested in targeting cancer metabolism in leukemia and shares findings published in his recent paper in Blood, “A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia:” https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020008955/475782/A-novel-and-highly-effective-mitochondrial

12:00 – Dr. Martinez asks about his thoughts regarding combination therapy

14:49 – Differences in immune response in younger patients

17:27 – Dr. Herranz provides a nice explanation of how his lab couples basic biology with a therapeutic approach

18:35 – Dr. Martinez explains his lab’s focus on modulating our own immune system’s response against the tumor cells

19:44 – They discuss the impact of ACS funding on their research and careers

23:07 – On improving diversity in cancer research and introducing younger students to science

In this episode, Gustavo Martinez, PhD, and Daniel Herranz, PhD, discussed their new cancer research publications. Dr. Martinez talked about his research into how T cells respond in the context of cancer, and Dr. Herrera explained his lab’s findings related to targeting cancer metabolism in leukemia.

Gustavo Martinez, PhD, is Assistant Professor at Rosalind Franklin University. He received American Cancer Society funding to support his research into T cell exhaustion and boosting our immune system’s response against cancer.

Daniel Herranz, PhD, is Assistant Professor of Pharmacology at Rutgers, The State University of New Jersey. His ACS-funded research focuses on T-cell acute lymphoblastic leukemia.

The first half of the conversation is more technical and is directed towards a scientific audience. The second part, starting at 17:27, is for all audiences.

1:38 – Dr. Martinez on the focus of his lab and takeaways from his recent publication in The Journal of Immunology titled, “Kdm6b Regulates the Generation of Effector CD8+ T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes:” https://www.jimmunol.org/content/early/2021/04/16/jimmunol.2001459

4:40 – What are some next steps? Are there downstream targets that could be activated?

7:54 – Dr. Herranz talks about why he’s interested in targeting cancer metabolism in leukemia and shares findings published in his recent paper in Blood, “A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia:” https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020008955/475782/A-novel-and-highly-effective-mitochondrial

12:00 – Dr. Martinez asks about his thoughts regarding combination therapy

14:49 – Differences in immune response in younger patients

17:27 – Dr. Herranz provides a nice explanation of how his lab couples basic biology with a therapeutic approach

18:35 – Dr. Martinez explains his lab’s focus on modulating our own immune system’s response against the tumor cells

19:44 – They discuss the impact of ACS funding on their research and careers

23:07 – On improving diversity in cancer research and introducing younger students to science

In this episode, Ran Li, PhD, and Daniel Heller, PhD, discuss new advances in using nanoparticles to deliver drugs to cancer cells.

Dr. Li was recently the first author of a paper in Nature Nanotech that described how cancer cells could be tricked into thinking they’re starved for nutrients, causing them to increase consumption of a cancer drug attached to the protein, albumin.

Dr. Heller published a review earlier this year that “highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs and, consequently, clinical outcomes.”

Ran Li, PhD, is an American Cancer Society – Ellison Foundation Postdoctoral Fellow and Instructor at Massachusetts General Hospital and Harvard Medical School.

Daniel Heller, PhD, is Associate Member at Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center. He is a two-time American Cancer Society grantee, having received a Postdoctoral Fellowship and Research Scholar Grant.

0:58 – Dr. Li describes new findings published in Nature Nanotech, “Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer:” https://www.nature.com/articles/s41565-021-00897-1

3:12 – Dr. Heller notes that “I’m a big fan of this paper and had my lab do a journal club on this,” and explains what he found exciting about it

5:46 –KRAS mutant cells are “ravenously thirsty,” making them susceptible to the approach taken by Dr. Li: “By tricking the cancer cells into thinking that they’ve been starved, they do more macropinocytosis, thereby taking more albumin-bound drug”

9:32 – “Do you think this could change how people use and prescribe this drug?”

11:50 – Dr. Heller shares some of the challenges and opportunities associated with nanoparticle drug delivery outlined in his review from earlier this year on targeted drug delivery strategies for precision medicines

16:34 – Dr. Li reacts…

18:29 – …and then asks, “What do you think a major hurdle is to bringing these novel drug delivery materials and technologies into the clinic?”

21:49 – On improvements that need to be made to nanomaterials in order to enhance precision medicine

In this episode, Ran Li, PhD, and Daniel Heller, PhD, discuss new advances in using nanoparticles to deliver drugs to cancer cells.

Dr. Li was recently the first author of a paper in Nature Nanotech that described how cancer cells could be tricked into thinking they’re starved for nutrients, causing them to increase consumption of a cancer drug attached to the protein, albumin.

Dr. Heller published a review earlier this year that “highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs and, consequently, clinical outcomes.”

Ran Li, PhD, is an American Cancer Society – Ellison Foundation Postdoctoral Fellow and Instructor at Massachusetts General Hospital and Harvard Medical School.

Daniel Heller, PhD, is Associate Member at Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center. He is a two-time American Cancer Society grantee, having received a Postdoctoral Fellowship and Research Scholar Grant.

0:58 – Dr. Li describes new findings published in Nature Nanotech, “Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer:” https://www.nature.com/articles/s41565-021-00897-1

3:12 – Dr. Heller notes that “I’m a big fan of this paper and had my lab do a journal club on this,” and explains what he found exciting about it

5:46 –KRAS mutant cells are “ravenously thirsty,” making them susceptible to the approach taken by Dr. Li: “By tricking the cancer cells into thinking that they’ve been starved, they do more macropinocytosis, thereby taking more albumin-bound drug”

9:32 – “Do you think this could change how people use and prescribe this drug?”

11:50 – Dr. Heller shares some of the challenges and opportunities associated with nanoparticle drug delivery outlined in his review from earlier this year on targeted drug delivery strategies for precision medicines

16:34 – Dr. Li reacts…

18:29 – …and then asks, “What do you think a major hurdle is to bringing these novel drug delivery materials and technologies into the clinic?”

21:49 – On improvements that need to be made to nanomaterials in order to enhance precision medicine

In this episode, two American Cancer Society grantees discuss recent findings related to how breast cancer patients feel about de-escalating chemotherapy as well as a new paper on comorbidities in breast cancer patients. The first half of the conversation is not necessarily technical, but it’s geared for a scientific audience. The second half is a more general discussion for a lay audience.

Avonne Connor, PhD, is a breast cancer epidemiologist focused on health disparities research. She is Assistant Professor of Epidemiology and Oncology at the Bloomberg School of Public Health and has a joint appointment at the Sidney Kimmel Comprehensive Cancer Center. She recently published findings in the journal Cancer on “Comorbidities and the risk of cardiovascular disease mortality among racially diverse patients with breast cancer:” https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33530

Gabrielle Rocque, MD, is a breast medical oncologist and health services researcher with an interest in quality and value in health care delivery. She is an Associate Professor of Medicine at The University of Alabama at Birmingham with joint appointments in hematology and oncology as well as gerontology, geriatrics, and palliative care. Her recent paper in Cancer Medicine was on “Patient perspectives on chemotherapy de‐escalation in breast cancer:” https://onlinelibrary.wiley.com/doi/10.1002/cam4.3891

3:02 – Dr. Rocque shares takeaways from her recent study on patients’ “interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation”

8:44 – How the pandemic influenced patients’ decisions

10:58 – How she became interested in exploring patient perspectives on de-escalating treatment

12:44 – Dr. Connor discusses findings on “associations between newly diagnosed comorbidities and the risk of cardiovascular disease mortality among (breast cancer) patients”

20:36 – Dr. Rocque reacts to the paper and asks, “Where do we go from here in terms of interventions?”

24:40 – On how a cancer diagnosis can prompt patients to reflect on their lives and how they can take care of their health

27:55 – Dr. Connor talks about how rewarding and exciting it is to train a postdoctoral fellow

29:39 – Dr. Rocque on her passion – how do we provide the best supportive care to patients, and how do we integrate research and clinical care?

30:50 – How American Cancer Society funding impacted their research and careers

In this episode, two American Cancer Society grantees discuss recent findings related to how breast cancer patients feel about de-escalating chemotherapy as well as a new paper on comorbidities in breast cancer patients. The first half of the conversation is not necessarily technical, but it’s geared for a scientific audience. The second half is a more general discussion for a lay audience.

Avonne Connor, PhD, is a breast cancer epidemiologist focused on health disparities research. She is Assistant Professor of Epidemiology and Oncology at the Bloomberg School of Public Health and has a joint appointment at the Sidney Kimmel Comprehensive Cancer Center. She recently published findings in the journal Cancer on “Comorbidities and the risk of cardiovascular disease mortality among racially diverse patients with breast cancer:” https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33530

Gabrielle Rocque, MD, is a breast medical oncologist and health services researcher with an interest in quality and value in health care delivery. She is an Associate Professor of Medicine at The University of Alabama at Birmingham with joint appointments in hematology and oncology as well as gerontology, geriatrics, and palliative care. Her recent paper in Cancer Medicine was on “Patient perspectives on chemotherapy de‐escalation in breast cancer:” https://onlinelibrary.wiley.com/doi/10.1002/cam4.3891

3:02 – Dr. Rocque shares takeaways from her recent study on patients’ “interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation”

8:44 – How the pandemic influenced patients’ decisions

10:58 – How she became interested in exploring patient perspectives on de-escalating treatment

12:44 – Dr. Connor discusses findings on “associations between newly diagnosed comorbidities and the risk of cardiovascular disease mortality among (breast cancer) patients”

20:36 – Dr. Rocque reacts to the paper and asks, “Where do we go from here in terms of interventions?”

24:40 – On how a cancer diagnosis can prompt patients to reflect on their lives and how they can take care of their health

27:55 – Dr. Connor talks about how rewarding and exciting it is to train a postdoctoral fellow

29:39 – Dr. Rocque on her passion – how do we provide the best supportive care to patients, and how do we integrate research and clinical care?

30:50 – How American Cancer Society funding impacted their research and careers

Finding out that a loved one has cancer can bring many changes. Doctors and nurses receive years of training in patient care, but family caregivers are often thrust into this role overnight with no training on the critical processes that their loved ones depend on them to do properly every day.

Rachel Cannady—as Strategic Director of Cancer Caregiver Support at the American Cancer Society—creates resources that empower caregivers with the resources and information they need.

Visit https://cancer.org/caregivers to learn more about what to expect if you become a caregiver for a person with cancer, and get tips for making sure that you take care of yourself as well.

Among the resources there are the Interactive Caregiver Resource Guide and the Caregiver Support Video Series.

The Interactive Caregiver Resource Guide is a comprehensive tool to help you learn how to care for yourself as a caregiver, better understand what your loved one is going through, and develop skills for coping and caring. It can be accessed or downloaded here: https://www.cancer.org/content/dam/cancer-org/cancer-control/en/booklets-flyers/american-cancer-society-caregiver-resource-guide.pdf

The Caregiver Support Video Series provides educational support to caregivers as they assist with the everyday needs of cancer patients and provide self-care techniques to improve their quality of life. Short videos provide guidance related to, for example, drain care, managing side effects, and managing medication. It’s available at https://www.cancer.org/treatment/caregivers/caregiver-support-videos.html.

2:20 – Creating evidence-informed resources for cancer caregivers

4:12 – On the village of cancer care in the United States

6:27 – “The bigger the village, the better the help” Some of the many responsibilities of cancer caregivers—information seeking, emotional support, decision making, navigating financial concerns, etc.

9:53 – On findings from the National Quality of Life Survey for Caregivers, a study that followed a group of caregivers over eight years

16:01 – “Nearly 50% of the caregivers at post-diagnosis said that they need help helping their loved one deal with the emotional stress of cancer.”

17:30 – There’s also a positive benefit from providing care – caregiving can create meaning in people’s lives

20:33 – The Caregiver Resource Guide, the Caregiver Support Video Series, and other resources developed through the American Cancer Society’s Caregiver Support Program

https://www.cancer.org/treatment/caregivers.html

29:16 – How these resources can empower caregivers and help them feel more confident, prepared, and at ease

31:20 – On the impact of COVID-19 on cancer caregiving