#290 ‒ Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

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Feb 19, 2024

Alex Aravanis, a trailblazer in DNA analysis and co-founder of Moonwalk Biosciences, dives into the future of cancer detection and aging research. He discusses the revolutionary impact of liquid biopsies for early cancer diagnosis, exploring cell-free DNA's role in improving specificity and sensitivity. Aravanis also unpacks the fascinating interplay of epigenetics and aging, including how cellular reprogramming may reverse age-related changes. His insights illuminate the cutting-edge intersection of technology, genetics, and health.

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ANECDOTE

Shared Engineering Background

Alex Aravanis and Peter Attia bonded over their shared engineering backgrounds in medical school.
Aravanis's PhD research involved applying engineering principles to neuroscience, specifically studying synaptic vesicles.

INSIGHT

Engineering Principles in Biology

A core principle from engineering, "if you can't build it, you don't understand it," applies to biology through experimentation.
Focus on experiments that guarantee new knowledge, regardless of hypothesis confirmation.

INSIGHT

Genome Sequencing Explained

Sequencing a genome means determining the order of 3 billion DNA bases (A, T, C, G).
Early genome sequencing involved laborious methods, later improved by miniaturization and parallel processing.

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Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging.

We discuss:

Alex’s background in applying engineering to problems in medicine [3:15];
A primer on human genetics, and the history and current landscape of DNA sequencing [11:00];
The advent and evolution of liquid biopsies for early detection of cancer [23:15];
The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15];
The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00];
Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00];
DNA methylation explained [58:15];
Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45];
The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00];
The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00];
Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45];
The role of epigenetics in aging [1:39:30];
How cell-free DNA methylation patterns can help identify a cancer’s tissue of origin [1:45:30];
Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and
More.

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