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ESMO Immuno-Oncology 2025 | Advances in in vivo screening to uncover cancer vulnerabilities

Dimitrios Garyfallos, PhD, University College London, London, UK, provides an overview of recent advancements in cancer biology, highlighting the potential of in vivo screens to provide a direct readout of tumor cell behavior within a living organism. This approach enables the functional validation of targets in vivo, allowing for the identification of genetic deletions that make cancer cells more vulnerable to immune cell attacks. This interview took place at 2025 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in London, UK.

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Transcript

So yeah, it’s actually a really exciting time to be in that field because in vivo screens are actually providing us with an unprecedented opportunity. So we have the capacity to have a direct readout of how tumor cells behave inside a living organism with an intact immune system. So traditionally, a lot of the discoveries in cancer biology were the result of very thorough investigation of cancer’s underlying molecular pathways...

So yeah, it’s actually a really exciting time to be in that field because in vivo screens are actually providing us with an unprecedented opportunity. So we have the capacity to have a direct readout of how tumor cells behave inside a living organism with an intact immune system. So traditionally, a lot of the discoveries in cancer biology were the result of very thorough investigation of cancer’s underlying molecular pathways. You would look for many years to understand interactions between different proteins, and you would try to design an inhibitor, let’s say, hoping for an effective treatment. Sometimes this would work, sometimes it wouldn’t, it wouldn’t validate. Instead of guessing or like making these very educated guesses about which genes matter, we can now watch tumors with thousands of different genetic deletions spanning across the entirety of the cancer cell genome, compete in real time within a living organism and see which knockouts make the cancer cell more vulnerable to immune cell attacks. So that means that drug discovery no longer starts with a theoretical target, but it starts with a target that has been effectively functionally validated in vivo. And of course, no technology is perfect, but such approaches have great potential in massively accelerating the pipeline of drug discovery.

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