Extreme intratumour heterogeneity and driver evolution in mismatch repair deficient gastro-oesophageal cancer

Loga, Katharina von; Woolston, Andrew; Punta, Marco; Barber, Louise J.; Griffiths, Beatrice; Semiannikova, Maria; Spain, Georgia; Challoner, Benjamin; Fenwick, Kerry; Schiffmann, Heiko; Marx, Andreas; Sauter, Guido; Lise, Stefano; Matthews, Nik; Gerlinger, Marco

doi:10.1101/755199

Cited by 1 publication

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“…In addition, mismatch repair-deficient tumours (e.g. gastro-oesophageal adenocarcinomas) are highly sensitive tumours to immunotherapy despite their extreme levels of genetic heterogeneity (von Loga et al, 2020). However, ambiguity remains on the role of immune system in cancer control.…”

Section: Major Theme 5: Cancer and The Immune Systemmentioning

confidence: 99%

Identifying key questions in the ecology and evolution of cancer

Dujon

Aktipis

Alix‐Panabières

et al. 2021

Evolutionary Applications

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The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50 years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco-evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed. Here, we aim to assess current advancements in the field and to suggest future directions for research.First, we summarize cancer research areas that, so far, have assimilated ecological and evolutionary principles into their approaches and illustrate their key importance. Then, we assembled 33 experts and identified 84 key questions, organized around nine major themes, to pave the foundations for research to come. We highlight the urgent need for broadening the portfolio of research directions to stimulate novel approaches at the interface of oncology and ecological and evolutionary sciences. We conclude that progressive and efficient cross-disciplinary collaborations that draw on the expertise of the fields of ecology, evolution and cancer are essential in order to efficiently address current and future questions about cancer. | INTRODUC TI ONThe application of evolutionary and ecological principles to preventing and treating cancer , as well as to understanding the impact of cancer on organismal health, fitness, species stability and ecosystem functioning (Thomas et al., 2017), has been gaining increasing attention and recognition among both oncologists and biologists since the seminal work of Cairns (1975), Nordling (1953 and Nowell (1976), more than 45 years ago. Most scientists today agree that this evolutionary view has deeply transformed the way we understand the biology of cancer-explaining its origin and the recrudescence of cancer cells as well as elucidating reasons for therapy failures. Following the theoretical development of a new interdisciplinary field that combines expertise from mathematicians, data scientists and biostatisticians, geneticists, evolutionary biologists, ecologists, physicists and oncologists, we are now at a pivotal point where empirical data and evidence are accumulating and guiding future directions of the discipline (Ujvari et al., 2017). We believe that the time has arrived to take stock of current advancements and to inform the course of future research. Cancer is a disease that impacts every country worldwide (18.1 million new cases and 9.6 million death in 2018; Bray et al., 2018), and these oncogenic processes are an inevitable phenomenon of metazoan life. Identifying the key questions in the ecology and evolution of cancer will provide a cornerstone in cancer and evolutionary research for the coming years. This will provide the basis for the development of efficient strategies to either preven...

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Section: Major Theme 5: Cancer and The Immune Systemmentioning

confidence: 99%