Mendelspod Podcast

Precision oncology is entering a new phase. Rather than simply profiling a tumor and matching it to a drug, physicians are increasingly able to follow a patient’s cancer over time, measuring treatment response, detecting residual disease, and adjusting therapy as the disease evolves.
Jerry Radich of Fred Hutch Cancer Center has been at the forefront of this evolution. His pioneering work in chronic myeloid leukemia (CML) helped establish molecular monitoring as a critical part of cancer care and prefigured the rise we see in MRD testing today. Some CML patients can even discontinue treatment after achieving a sustained deep molecular response. Radich discusses how this remarkable success has become a model for other blood cancers.
He’s now helping lead myeloMATCH, a national precision oncology initiative that brings together clinical trial groups across North America. With some 350 participating sites and molecular results typically available in less than 48 hours, the program is matching patients with acute myeloid leukemia to clinical trials based on their cancer’s genetic profile. Radich sees an opportunity not only to personalize treatment but to accelerate drug development by using molecular response as an earlier measure of efficacy.
We also explore the limits of molecular profiling, the emerging role of the immune system, and why increasingly sensitive tests may transform how we understand cancer. Looking ahead, Radich imagines a future in which patients could monitor their disease burden almost continuously, perhaps even through wearable or implantable devices.
Radich is co-chairing the upcoming APOAPE conference in Seattle on January 15, bringing oncologists and pathologists together to connect advances in molecular diagnostics with real-world treatment decisions. The conference is free for healthcare professionals.
Learn more about the APOAPE conference


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In the US, we have the All of Us Research Program. In the UK, they have Our Future Health, an ambitious new population health research program that aims to make healthcare more preventive than reactive. Launched just four years ago, it has already recruited nearly three million volunteers toward a goal of five million, making it one of the world’s largest health research initiatives.
Today we’re joined by Raghib Ali, CEO and Principal Investigator of Our Future Health, to discuss how the program builds on the success of UK Biobank while pursuing a different goal. Rather than simply studying the causes of disease, Our Future Health aims to establish the evidence needed to move healthcare from diagnosis and treatment toward prediction and prevention.
Ali discusses the program’s plans to combine polygenic risk scores with clinical and lifestyle data to develop integrated disease risk scores. A new clinical trials platform will test whether personalized prevention actually improves outcomes. The ultimate ambition is to bring successful approaches into routine NHS care.
Perhaps most encouraging is the public response. More than a million participants have come from historically underrepresented groups, raising the possibility that precision medicine could help reduce health inequalities rather than widen them.
As Ali puts it, the goal is to move from a national sickness service to a true national health service.


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In recent months on Mendelspod, we’ve explored how new sequencing and proteomics technologies are revealing biology in regions of the genome (and proteome) that have long escaped our attention. From repeat expansion disorders to new approaches in cancer diagnostics, the dark genome is increasingly becoming clinically relevant.
Today we’re revisiting a conversation from earlier in the year that asks an even bigger question. What if much of this unexplored genomic territory is not simply functional, but a reservoir of evolutionary possibility?
Last March, we talked with Sudhakaran Prabakaran, computational biologist at Northeastern University, founder of NonExomics, and author of Eclipsed Horizons: Unveiling the Dark Genome.
Drawing on his lab’s work cataloging more than 250,000 non-canonical proteins, Prabakaran argued that regions outside traditional gene definitions may be continually generating new proteins with implications for adaptation, evolution, and disease.
From rapidly diversifying cichlid fishes to human accelerated regions (HARs) of the human genome linked to schizophrenia, Sudhakaran makes the case that protein birth and death is continuous, cheap, and exploratory. In his framing, the “dark genome” functions less like debris and more like a flexible evolutionary sandbox. His company, NonExomics, is also exploring how these previously overlooked proteins might become biomarkers for cancer and other diseases.
As our recent interviews have demonstrated, we’re entering a new era of genomic discovery. Prabakaran challenges us to think about just how much biology remains to be found.


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Repeat expansions are places where the genome has remained stubbornly dark. Long-read sequencing is beginning to illuminate them, and now that new visibility is moving into clinical testing.
Today we’re joined by Simon Sadedin, Head of Clinical Bioinformatics at Victorian Clinical Genetics Services in Australia, and Alex Lindell, Senior Director of Product Marketing at Oxford Nanopore.
Until now, testing for repeat expansions has largely meant building a separate assay for each disorder. A patient might be tested for Fragile X, get a negative result, and then move on to another test, sometimes waiting months at each step. Some repeat expansions have been difficult to test for at all. Simon’s group is trying to replace that serial approach with a single assay covering roughly 60 repeat expansion loci, which is now being submitted for clinical accreditation.
The promise goes beyond simply finding an expansion. Long reads can reveal its length, sequence, methylation and mosaicism, while adaptive sampling makes it possible to target these difficult regions in software rather than building a new wet lab assay for each one.
Some say we are at a new threshold in genomics, where parts of the genome that have remained dark are finally becoming accessible to both discovery and clinical medicine.


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Sometimes the best evidence that a new medical technology is working is simply that doctors start depending on it. For years, the promise of molecular medicine has been that better genomic information would lead to better patient care. At Roswell Park Comprehensive Cancer Center, Vice Chair of Molecular Pathology, Sean Glenn, offers a compelling example of that promise becoming routine clinical practice.
Hematologic cancers can require information from many different kinds of genomic alterations and traditionally from multiple tests and laboratories. Glenn and his team developed a comprehensive pan-hematological assay that brings much of that information together, using both DNA and RNA to detect alterations across myeloid and lymphoid cancers. The panel targets nearly 400 genes on the DNA side and about 125 on the RNA side, while automation has helped Roswell Park achieve an average turnaround time of roughly two and a half days for the 50 to 60 tests it runs each week.
And the oncologists are depending on it. Since introducing the panel, Glenn says Roswell Park has seen “a transformation and a resurgence of clinical care” in its leukemia and lymphoma clinics. His favorite measure of success is wonderfully practical. The oncologists are no longer calling the lab every few days asking where their results are. The information simply arrives in the patient’s record, in time to help make treatment decisions.


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