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Landmark discoveries, like EGFR mutations, didn't start in a lab but with astute oncologists noticing patterns in how some patients responded to treatment while others didn't. This highlights that every patient interaction is a research opportunity, offering clues that can lead to the next scientific breakthrough.

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Despite rigid protocols, investigators must use their clinical judgment, informed by prior data, to enroll patients they believe will genuinely benefit. This patient-centric approach is viewed as not only ethical but also crucial for achieving a positive trial outcome, blending the art of medicine with the science of research.

Progress in drug development often hides inside failures. A therapy that fails in one clinical trial can provide critical scientific learnings. One company leveraged insights from a failed study to redesign a subsequent trial, which was successful and led to the drug's approval.

Dr. Radvanyi emphasizes that foundational discoveries in immunotherapy arose from basic immunology and serendipitous observations, like his own unexpected T-cell proliferation with an anti-CTLA-4 antibody. This highlights the risk of over-prioritizing translational research at the expense of fundamental, curiosity-driven science.

In oncology R&D, a successful two-drug combination isn't the final goal but the new standard of care to build upon. Researchers immediately begin planning for "triplets"—adding a third agent to the successful doublet—demonstrating a relentless, forward-looking strategy to incrementally improve patient outcomes.

A crucial piece of advice for biotech founders is to interact with patients as early as possible. This 'patient first' approach helps uncover unmet needs in their treatment journey, providing a more powerful and differentiated perspective than focusing solely on the scientific or commercial landscape.

A successful research program requires deep integration with the clinical environment. By spending time with oncologists and nurses and joining tumor boards, scientists gain the necessary context to ask the most meaningful questions, bridging the gap between theoretical lab work and the reality of patient care.

True scientific advancement happens when researchers refuse to accept 'no' as an answer. When immunotherapy was dismissed for lung cancer, pioneers investigated why it worked in melanoma but not other cancers. This mindset—questioning failures and studying successes—is key to turning scientific impossibilities into standard treatments.

The technology for detecting cancer via cell-free DNA was discovered by accident. During non-invasive prenatal tests, some abnormal results weren't from the baby but from the mother's previously undiagnosed tumors shedding DNA, revealing an entirely new application for the technology.

Biomarkers provide value beyond predicting patient response. Their core function is to answer 'why' a treatment succeeded or failed. This explanatory power informs sequential therapy decisions and provides crucial scientific insights that advance the entire medical field, not just the individual patient's case.

The most impactful medical advances come from 'clinical scientists' who both see patients and work in the lab. This dual perspective provides a deep understanding of disease mechanisms and how to translate research into treatments, a model that Dr. Abelson believes is now under threat due to economic pressures.

Major Cancer Breakthroughs Stem from Clinicians' Everyday Patient Observations | RiffOn