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Review
. 2022 May;43(5):379-390.
doi: 10.1016/j.it.2022.03.003. Epub 2022 Apr 1.

All is not lost: learning from 9p21 loss in cancer

Pavlina Spiliopoulou  1 , S Y Cindy Yang  1 , Jeff P Bruce  1 , Ben X Wang  1 , Hal K Berman  2 , Trevor J Pugh  3 , Lillian L Siu  4
Affiliations
Free article
Review

All is not lost: learning from 9p21 loss in cancer

Pavlina Spiliopoulou et al. Trends Immunol. 2022 May.
Free article

Abstract

The cancer research community continues to search for additional biomarkers of response and resistance to immune checkpoint treatment (ICT). The ultimate goal is to direct the use of ICT in patients whose tumors are most likely to benefit to achieve a refinement that is equivalent to that of a genotype-matched targeted treatment. Dissecting the mechanisms of ICT resistance can help us characterize ICT nonresponders more efficiently. In this opinion, we argue that there may be additional knowledge gained about immune evasion in cancer by analyzing the loss of the human 9p21.3 locus; as an example, we highlight findings of 9p21.3 loss from the investigator-initiated, pan-cancer INSPIRE study, in which patients were treated with pembrolizumab (anti-PD-1 antibody) ICT.

Keywords: 9p21.3 loss; CDKN2A/B; MTAP; cancer immunotherapy; treatment resistance biomarkers; tumour microenvironment.

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Conflict of interest statement

Declaration of interests P.S., S.Y.C.Y, J.P.B. and H.K.B. have nothing to declare. B.X.W. has received honoraria from AstraZeneca and Tessa Therapeutics. T.J.P. provides consultation for Illumina, Merck, Chrysalis Biomedical Advisors and the Canadian Pension Plan Investment Board (compensated); and receives research support (institutional) from Roche/Genentech. L.L.S. has consulting/advisory arrangements with Merck, Pfizer, AstraZeneca, Roche, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, Daiichi Sanyko, Coherus, Marengo, and InteRNA; stock ownership of Agios (spouse); a leadership position in Treadwell Therapeutics (spouse); and their institution receives clinical trials support from Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Intensity Therapeutics, Mirati Therapeutics, and Shattucks.

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