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. 2023 Jun 5;29(6):1400–1411. doi: 10.1038/s41591-023-02399-0

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, SNIPRx CRISPR–Cas9-enabled chemogenomic screen to identify ATRi-sensitizing and synthetic lethal alterations for patient selection. b, Patient enrollment by gene and tumor type and overview of pre-planned analyses, which included (1) clinical endpoints; (2) PK in plasma and PD in pre-treatment and on-treatment biopsies; (3) hypothesis-generating genomic analyses, such as the assessment of allelic status (that is, biallelic versus non-biallelic alterations) and somatic versus germline status; and (4) analysis of longitudinal ctDNA as an early marker of camonsertib activity. c, CONSORT diagram of TRESR monotherapy patient populations. Patients enrolled in M1c received a single dose on day 3 in the fed state and continued from day 1 (fasted state) on either the 5/2 (n = 3) or 3/4 (n = 9) schedule. 3/4, 3 d on, 4 d off; 5/2, 5 d on, 2 d off; CN, copy number; CRC, colorectal cancer; HomDel, homozygous deletion; M, module; TCGA, The Cancer Genome Atlas; Tx, therapy.