American Cancer Society scientists and grantees discuss the most critical questions in cancer research -- in language that we can all understand.
Maximizing what's learned from clinical trials in children
The St. Baldrick's Foundation, the largest charitable funder of childhood cancer research grants, and the American Cancer Society, a health organization dedicated to eliminating cancer, formed a partnership in 2019 to fund grants that will accelerate childhood cancer research with the goals of understanding and discovering new treatment options and improving care and survival in children with cancer.
Kathleen Ruddy, St. Baldrick’s Foundation CEO, joined the podcast to talk through the goals of this unique partnership. “Why do some patients respond better than others to a particular treatment? Why does one treatment cause more late effects than another? What else can we learn to speed up progress, to cure more children, more effectively, and less harshly?”
Then two of the grantees who have been funded through the partnership talked about what they hope to accomplish.
Yael P. Mossé, MD, is Associate Professor of Pediatrics at the University of Pennsylvania and Director of the Neuroblastoma Developmental Therapeutics Program, as well as a pediatric oncologist at The Children's Hospital of Philadelphia. Dr. Mossé’s grant is focused on improving patient outcomes for ALK mutant neuroblastoma through precision molecular targeting.
E. Anders Kolb, MD, is Vice Chairman for Research and Professor in the Department of Pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University, as well as Director of the Nemours Center for Cancer and Blood Disorders at Nemours/Alfred I. duPont Hospital for Children. Dr. Kolb’s study aims to validate the detection of novel biomarkers for the Pediatric Acute Leukemia (PedAL) Initiative Sub-trials.
0:00 – Kathleen Ruddy, CEO of St. Baldrick’s Foundation
10:25 – Yael P. Mossé, MD, and E. Anders Kolb, MD
11:29 – Drs. Mossé and Kolb on why, “in pediatric cancer care, clinical trial participation is the standard of care”
13:31 – Dr. Mossé on how her team is “bringing the science to the patient” to learn how children with neuroblastoma respond (or don’t respond) to treatments
15:57 – Dr. Kolb on why it’s so important, and challenging, to bring precision medicine approaches to childhood cancer treatment
18:37 –Dr. Mossé explains the goal “to bring the science to the clinical trials in real time and not for there to be a lag”
21:38 – Dr. Kolb highlights how revolutionary it is for Dr. Mossé to change a clinical trial based on data emerging in the lab
23:26 – Dr. Kolb explains how “the AML that kids get is nothing like the AML that older adults get” and why this matters for drug development
27:43 – “We as pediatricians are taught early on,” notes Dr. Mossé, “that kids are not small adults, and it really is the same for pediatric cancer.”
30:17 – Dr. Kolb on the inspiration he drew from an initiative by St. Baldrick’s Foundation called Project:EveryChild, and describes his new study: “what we hope is that we will be as successful in relapse as we have been in newly diagnosed AML”
32:25 – Dr. Mossé on the value of collecting tissue over time, including at relapse, and how a major part of her new study is using liquid biopsies to collect samples in a less invasive way
34:43 – Dr. Kolb on the impact of this funding: “If we’re successful, we’re going to be able to rapidly screen for relevant biomarkers and we’re going to be able to enroll kids in the therapy that has the highest potential to provide benefit.”
37:46 – Dr. Mossé describes how this funding will support her research: “My hope and my expectation is to make a really big difference for a small subset of patients. I think that’s where cancer biology has turned now—one disease is not defined by its histology; it’s defined by its underlying molecular biology.”
40:29 – A message they’d like to share with children going t
“Overstretched & Overlooked: Solving challenges faced by early-career scientists after the pandemic”
A new publication by six current and former American Cancer Society grantees describes the challenges faced by early-career investigators as a result of the pandemic and offers recommendations “to help institutions and individuals develop effective strategies to promote success and career advancement.”
They joined the TheoryLab podcast to talk about key takeaways from their article, which “highlights the aftermath of the pandemic on work–life balance, promotion, tenure, funding, networking, and mentoring, and make recommendations that can help remediate these problems.”
“Overstretched and overlooked: solving challenges faced by early-career investigators after the pandemic” was published in the journal Trends in Cancer: (https://www.cell.com/trends/cancer/fulltext/S2405-8033(21)00158-8)
3:41 – Brock Humphries, PhD, is a postdoctoral fellow at the University of Michigan.
Priscilla Hwang, PhD, is an Assistant Professor in Biomedical Engineering at Virginia Commonwealth University.
Aga Kendrick, PhD, is a postdoctoral fellow at University of California, San Diego Medical Center.
Rajan Kulkarni, MD, PhD, is an Associate Professor of Dermatology at Oregon Health and Science University.
Rachel Pozzar, PhD, is a nurse scientist at Dana-Farber Cancer Institute and Instructor of Medicine at Harvard Medical School.
Rebeca San Martin, PhD, is a postdoctoral fellow at the University of Tennessee, Knoxville.
5:10 – What does it mean to be an “early-stage cancer researcher?”
9:56 – The unique challenges faced by early-career scientists
15:01 – How the American Cancer Society encouraged a conversation about how to surmount these challenges
16:33 – Some of the most striking things they learned from each other
22:47 – Productivity issues faced by early-stage researchers
24:19 – How cancer research labs have functioned during the pandemic
29:35 – How the pandemic has impacted the tenure clock for clinician scientists
34:21 – Ways to promote mental health among early-career investigators
37:36 – Some concluding thoughts about improving the environment for early-stage cancer researchers
40:26 – Their message for cancer patients, survivors, and caregivers
Catching the problem early: The early stages of lung cancer initiation & melanoma drug resistance
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
Under pressure: Compression and crowding inside cancer cells
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
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
Modulating the immune response to cancer & using metabolic routes in leukemia to our advantage
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
Tricking cancer cells into taking drugs & improving drug delivery strategies for precision medicines
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
ACS funds the best science
I’m so proud to work for the American Cancer Society! As non scientific staff, I enjoy learning about cancer research through TheoryLab.
Diverse topics, scientifically a bit shallow
Interesting podcast that covers a wide range of topics in cancer research. Only criticism is the scientific discussion is tailored to a very broad audience. A bit more Scientific rigor and detail would make it 5 stars in my book. Please keep it up!
How many hope lodge patients had to stop treatment as you escorted them home ?