Branco Weiss Fellow Since
2022
Research Category
Epigenetics, Cancer Biology, Evolution
Research Location
Cancer Research UK Cambridge Institute, University of Cambridge, United Kingdom
Background
The emergence of therapy resistance in metastatic cancer – wherein tumor cells from a primary site progressively colonize distant organs – impedes curative therapy and results in patient relapse. It is known that resistance can be caused by genetic mutations, but in some cases, there is no clear genetic basis, suggesting that non-genetic (i.e. epigenetic) mechanisms might drive resistance. Epigenetic mechanisms may drive therapy resistance in cancer cells through formation of epimutations – changes in gene expression that are independent of changes in DNA sequence. Such epimutations may provide initial tolerance, allowing a fraction of tumor cells to survive and later acquire secondary genetic mutations that drive disease progression to relapse. Epimutations have been proposed to facilitate adaptive phenotypic responses to external insults, but experimental evidence is scarce. Dr. Sito Torres-Garcia’s research demonstrated that epimutations can drive environmental adaptation in fission yeast, but whether similar mechanisms play a role in complex mammalian systems such as cancer remains elusive.
Details of Research
Dr. Sito Torres-Garcia will investigate the potential for epimutations to prime adaptive evolution in metastatic cancer. Taking a cross-disciplinary approach, he will blend novel laboratory models with innovative experimental and computational methodologies to study cancer progression under standard-of-care therapy at unprecedent detail. He will then maximise the translational impact of his research by implementing newly acquired knowledge into clinically relevant models. Dr. Torres-Garcia’s project aims to unravel conserved epigenetic mechanisms that drive therapy resistance in metastatic cancer, but also general adaptation to stress in mammalian cells. Understanding these mechanisms could shed light on broad principles of eukaryotic adaptation and reveal potential therapeutic opportunities to improve patient outcome.
