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Editorial
. 2022 Jul 6;12(7):1612-1614.
doi: 10.1158/2159-8290.CD-22-0492.

Inducing Hypermutability to Promote Anti-PD-1 Therapy Response

Jason A Willis  1   2 , Michael J Overman  1
Affiliations
Editorial

Inducing Hypermutability to Promote Anti-PD-1 Therapy Response

Jason A Willis et al. Cancer Discov. .

Abstract

The lack of clinical activity from various immune-checkpoint blockade approaches in mismatch repair- proficient (MMRp) colorectal cancer has demonstrated a critical need for novel approaches. In this issue, Crisafulli and colleagues provide proof of concept for the induction of hypermutability through the use of temozolomide as a potential pathway for enabling a productive anti-PD-1 immune response in MMRp colorectal cancer. See related article by Crisafulli et al., p. 1656 (1) .

Trial registration: ClinicalTrials.gov NCT03519412.

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References

    1. Crisafulli G, Sartore-Bianchi A, Lazzari L, Pietrantonio F, Amatu A, Macagno M, et al. Temozolomide treatment alters mismatch repair and boosts mutational burden in tumor and blood of colorectal cancer patients. Cancer Discov 2022;12:1656–75. - PMC - PubMed
    1. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409–13. - PMC - PubMed
    1. Alexandrov LB, Kim J, Haradhvala NJ, Huang MN, Tian Ng AW, Wu Y, et al. The repertoire of mutational signatures in human cancer. Nature 2020;578:94–101. - PMC - PubMed
    1. Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, et al. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 2006;66:3987–91. - PMC - PubMed
    1. Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, et al. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 2007;13:2038–45. - PMC - PubMed

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