{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:56:32Z","timestamp":1792112192143,"version":"4.4.0"},"reference-count":58,"publisher":"American Association for Cancer Research (AACR)","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":104,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101020342"],"award-info":[{"award-number":["101020342"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["21091"],"award-info":[{"award-number":["21091"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["28922"],"award-info":[{"award-number":["28922"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["31560"],"award-info":[{"award-number":["31560"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["31358"],"award-info":[{"award-number":["31358"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>DNA mismatch repair (MMR) detects and corrects postreplicative DNA alterations; it is deregulated in up to 20% of human cancers. MMR-deficient (MMR-d) cancers display increased tumor mutational burden (TMB) and microsatellite instability (MSI) and are eligible for checkpoint inhibitor (CPI) immunotherapy which commonly elicits durable responses. We reasoned that pharmacologic blockade of MMR could broaden the patient population eligible for immunotherapy. Here, we reveal MMR protein PMS2 as a druggable target and describe the discovery and characterization of first-in-class small-molecule MMR pathway modulator NP1867. In vitro treatment of murine cancer cells abrogates MMR function and elicits an MMR-d genotype, including increased TMB, MMR-d mutational signatures, and MSI-high (MSI-H) status. Inoculation of syngeneic immunocompetent mice with cancer cells pretreated with NP1867 leads to CPI sensitivity, tumor growth delay, and complete responses. For the first time, we demonstrate pharmacologic targeting of MMR to proactively rewire the tumor\u2013host relationship for therapeutic purposes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We present the discovery and characterization of NP1867, a selective covalent small-molecule inhibitor of MMR protein PMS2. Pharmacologic blockade of PMS2 leads to an MMR-deficient genotype characterized by increased TMB, enriched MMR-d mutational signatures, and MSI-H status. Treatment with NP1867 converts immunoresistant, MMR-proficient cancers into CPI-responsive tumors.<\/jats:p>\n                    <jats:p>See related commentary by Bernards, p. 1486<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-26-0003","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T20:01:56Z","timestamp":1776801716000},"page":"1649-1665","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacologic Inhibition of PMS2 Induces MMR Deficiency and Response to Immune Checkpoint Blockade"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-0323","authenticated-orcid":false,"given":"Julian","family":"Blagg","sequence":"first","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7227-9116","authenticated-orcid":false,"given":"Philippe","family":"Riou","sequence":"additional","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-6678","authenticated-orcid":false,"given":"Alexia","family":"Hervieu","sequence":"additional","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6766-0257","authenticated-orcid":false,"given":"Eleonora","family":"Piumatti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Torino 3 Department of Oncology, Molecular Biotechnology Center, , Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5046-2410","authenticated-orcid":false,"given":"Maria T.","family":"Rodriguez-Plata","sequence":"additional","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3816-1881","authenticated-orcid":false,"given":"Paolo","family":"Battuello","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Torino 3 Department of Oncology, Molecular Biotechnology Center, , Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8537-2905","authenticated-orcid":false,"given":"Adam","family":"Peall","sequence":"additional","affiliation":[{"name":"4Charnwood Discovery, Loughborough, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-4399","authenticated-orcid":false,"given":"Vito","family":"Amodio","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Torino 3 Department of Oncology, Molecular Biotechnology Center, , Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-7662","authenticated-orcid":false,"given":"Pietro Paolo","family":"Vitiello","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Torino 3 Department of Oncology, Molecular Biotechnology Center, , Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0901-6910","authenticated-orcid":false,"given":"Daniel J.H.","family":"Nightingale","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3634-557X","authenticated-orcid":false,"given":"Ruzica","family":"Bago","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6334-6409","authenticated-orcid":false,"given":"Paige","family":"Tongue","sequence":"additional","affiliation":[{"name":"4Charnwood Discovery, Loughborough, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4012-8828","authenticated-orcid":false,"given":"Tessa","family":"Slater","sequence":"additional","affiliation":[{"name":"4Charnwood Discovery, Loughborough, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4755-6326","authenticated-orcid":false,"given":"Kalpesh","family":"Parmar","sequence":"additional","affiliation":[{"name":"6o2h Discovery Pvt Ltd, Ahmedabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1394-0598","authenticated-orcid":false,"given":"Pradip","family":"Patel","sequence":"additional","affiliation":[{"name":"6o2h Discovery Pvt Ltd, Ahmedabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-7828","authenticated-orcid":false,"given":"Javier","family":"Rodr\u00edguez Gonz\u00e1lez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"McGill University 7 Department of Biochemistry, Centre de Recherche en Biologie Structurale, , Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-1893","authenticated-orcid":false,"given":"David E.","family":"Clark","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-3712","authenticated-orcid":false,"given":"Gareth W.","family":"Langley","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-371X","authenticated-orcid":false,"given":"Charles","family":"Nichols","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-9132","authenticated-orcid":false,"given":"Alba","family":"Guarn\u00e9","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"McGill University 7 Department of Biochemistry, Centre de Recherche en Biologie Structurale, , Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7857-6224","authenticated-orcid":false,"given":"Paul C.M.","family":"Winship","sequence":"additional","affiliation":[{"name":"5Charles River Laboratories, Saffron Walden, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9818-9134","authenticated-orcid":false,"given":"Matthew","family":"Baker","sequence":"additional","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-0556","authenticated-orcid":false,"given":"Martin","family":"Drysdale","sequence":"additional","affiliation":[{"name":"1NeoPhore Ltd, Altrincham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-8684","authenticated-orcid":false,"given":"Giovanni","family":"Germano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Milano 8 Department of Medical Biotechnology and Translational Medicine, , Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1647-5070","authenticated-orcid":false,"given":"Alberto","family":"Bardelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hcsa680","id-type":"ROR","asserted-by":"publisher"}],"name":"IFOM ETS - The AIRC Institute of Molecular Oncology 2 , Milan, Italy."},{"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Torino 3 Department of Oncology, Molecular Biotechnology Center, , Turin, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026080303135906000_bib1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/s41571-025-01054-6","article-title":"Therapeutic targeting of mismatch repair-deficient cancers","volume":"22","author":"Johannet","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"2026080303135906000_bib2","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1158\/2159-8290.CD-18-0150","article-title":"The clinical impact of the genomic landscape of mismatch repair-deficient cancers","volume":"8","author":"Germano","year":"2018","journal-title":"Cancer Discov"},{"key":"2026080303135906000_bib3","doi-asserted-by":"crossref","first-page":"26395","DOI":"10.1074\/jbc.R115.660142","article-title":"Mismatch repair","volume":"290","author":"Fishel","year":"2015","journal-title":"J Biol Chem"},{"key":"2026080303135906000_bib4","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.mrrev.2017.07.001","article-title":"DNA mismatch repair and its many roles in eukaryotic cells","volume":"773","author":"Liu","year":"2017","journal-title":"Mutat Res Rev Mutat Res"},{"key":"2026080303135906000_bib5","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1073\/pnas.1914718117","article-title":"Human MutL\u03b3, the MLH1-MLH3 heterodimer, is an endonuclease that promotes DNA expansion","volume":"117","author":"Kadyrova","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026080303135906000_bib6","doi-asserted-by":"crossref","first-page":"e21900","DOI":"10.7554\/eLife.21900","article-title":"Concerted action of the MutL\u03b2 heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion","volume":"6","author":"Duroc","year":"2017","journal-title":"Elife"},{"key":"2026080303135906000_bib7","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1101\/gr.148718.112","article-title":"The origin, evolution, and functional impact of short insertion-deletion variants identified in 179 human genomes","volume":"23","author":"Montgomery","year":"2013","journal-title":"Genome Res"},{"key":"2026080303135906000_bib8","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrg1348","article-title":"Microsatellites: simple sequences with complex evolution","volume":"5","author":"Ellegren","year":"2004","journal-title":"Nat Rev Genet"},{"key":"2026080303135906000_bib9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability","volume":"96","author":"Umar","year":"2004","journal-title":"J Natl Cancer Inst"},{"key":"2026080303135906000_bib10","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1056\/NEJMp1709968","article-title":"First FDA approval agnostic of cancer site - when a biomarker defines the indication","volume":"377","author":"Lemery","year":"2017","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"2026080303135906000_bib12","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib13","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1056\/NEJMoa2216334","article-title":"Dostarlimab for primary advanced or recurrent endometrial cancer","volume":"388","author":"Mirza","year":"2023","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib14","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1056\/NEJMoa2402141","article-title":"Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer","volume":"391","author":"Andre","year":"2024","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib15","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1056\/NEJMoa2400634","article-title":"Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer","volume":"390","author":"Chalabi","year":"2024","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib16","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib17","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1056\/NEJMoa2404512","article-title":"Nonoperative management of mismatch repair-deficient tumors","volume":"392","author":"Cercek","year":"2025","journal-title":"N Engl J Med"},{"key":"2026080303135906000_bib18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41575-019-0126-x","article-title":"Immunotherapy in colorectal cancer: rationale, challenges and potential","volume":"16","author":"Ganesh","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026080303135906000_bib19","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1038\/s41591-024-03083-7","article-title":"Botensilimab plus balstilimab in relapsed\/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial","volume":"30","author":"Bullock","year":"2024","journal-title":"Nat Med"},{"key":"2026080303135906000_bib20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41571-022-00718-x","article-title":"At the crossroads of immunotherapy for oncogene-addicted subsets of NSCLC","volume":"20","author":"Otano","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"2026080303135906000_bib21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"2026080303135906000_bib22","doi-asserted-by":"crossref","first-page":"e006533","DOI":"10.1136\/jitc-2022-006533","article-title":"Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies","volume":"11","author":"Anderson","year":"2023","journal-title":"J Immunother Cancer"},{"key":"2026080303135906000_bib23","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1158\/0008-5472.CAN-25-2255","article-title":"Mismatch repair as a dynamic and clinically actionable vulnerability in cancer","volume":"85","author":"Piumatti","year":"2025","journal-title":"Cancer Res"},{"key":"2026080303135906000_bib24","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature24673","article-title":"Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth","volume":"552","author":"Germano","year":"2017","journal-title":"Nature"},{"key":"2026080303135906000_bib25","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1126\/science.aau0447","article-title":"Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response","volume":"364","author":"Mandal","year":"2019","journal-title":"Science"},{"key":"2026080303135906000_bib26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ccell.2022.12.003","article-title":"Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance","volume":"41","author":"Amodio","year":"2023","journal-title":"Cancer Cell"},{"key":"2026080303135906000_bib27","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1021\/acs.jmedchem.9b00940","article-title":"Heat shock protein 90 inhibitors: an update on achievements, challenges, and future directions","volume":"63","author":"Li","year":"2020","journal-title":"J Med Chem"},{"key":"2026080303135906000_bib28","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/mc.20514","article-title":"Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key","volume":"48","author":"Leong","year":"2009","journal-title":"Mol Carcinog"},{"key":"2026080303135906000_bib29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0092-8674(00)81621-9","article-title":"Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis","volume":"95","author":"Ban","year":"1998","journal-title":"Cell"},{"key":"2026080303135906000_bib30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0092-8674(00)80717-5","article-title":"Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair","volume":"97","author":"Ban","year":"1999","journal-title":"Cell"},{"key":"2026080303135906000_bib31","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1158\/1078-0432.CCR-11-1000","article-title":"Hsp90 molecular chaperone inhibitors: are we there yet?","volume":"18","author":"Neckers","year":"2012","journal-title":"Clin Cancer Res"},{"key":"2026080303135906000_bib32","doi-asserted-by":"crossref","first-page":"21810","DOI":"10.1074\/jbc.M108787200","article-title":"Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha","volume":"277","author":"R\u00e4schle","year":"2002","journal-title":"J Biol Chem"},{"key":"2026080303135906000_bib33","doi-asserted-by":"crossref","first-page":"9297","DOI":"10.1021\/acs.jmedchem.3c00550","article-title":"Expanding chemical probe space: quality criteria for covalent and degrader probes","volume":"66","author":"Hartung","year":"2023","journal-title":"J Med Chem"},{"key":"2026080303135906000_bib34","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.1093\/emboj\/20.19.5521","article-title":"Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase","volume":"20","author":"Guarn\u00e9","year":"2001","journal-title":"EMBO J"},{"key":"2026080303135906000_bib35","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1021\/acs.biochem.5b00148","article-title":"ATP acyl phosphate reactivity reveals native conformations of Hsp90 paralogs and inhibitor target engagement","volume":"54","author":"Nordin","year":"2015","journal-title":"Biochemistry"},{"key":"2026080303135906000_bib36","first-page":"2327","article-title":"DNA mismatch repair (MMR) mediates 6-thioguanine genotoxicity by introducing single-strand breaks to signal a G2-M arrest in MMR-proficient RKO cells","volume":"9","author":"Yan","year":"2003","journal-title":"Clin Cancer Res"},{"key":"2026080303135906000_bib37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"2026080303135906000_bib38","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"2026080303135906000_bib39","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/bioinformatics\/btt755","article-title":"MSIsensor: microsatellite instability detection using paired tumor-normal sequence data","volume":"30","author":"Niu","year":"2014","journal-title":"Bioinformatics"},{"key":"2026080303135906000_bib40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coph.2014.07.007","article-title":"Chemical biology approaches to target validation in cancer","volume":"17","author":"Blagg","year":"2014","journal-title":"Curr Opin Pharmacol"},{"key":"2026080303135906000_bib41","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1093\/carcin\/19.11.1931","article-title":"Resistance to 6-thioguanine in mismatch repair-deficient human cancer cell lines correlates with an increase in induced mutations at the HPRT locus","volume":"19","author":"Glaab","year":"1998","journal-title":"Carcinogenesis"},{"key":"2026080303135906000_bib42","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1158\/2159-8290.CD-21-1434","article-title":"Temozolomide treatment alters mismatch repair and boosts mutational burden in tumor and blood of colorectal cancer patients","volume":"12","author":"Crisafulli","year":"2022","journal-title":"Cancer Discov"},{"key":"2026080303135906000_bib43","doi-asserted-by":"crossref","first-page":"e005059","DOI":"10.1136\/jitc-2022-005059","article-title":"Overcoming resistance to \u03b1PD-1 of MMR-deficient tumors with high tumor-induced neutrophils levels by combination of \u03b1CTLA-4 and \u03b1PD-1 blockers","volume":"10","author":"Nebot-Bral","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2026080303135906000_bib44","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S1470-2045(24)00026-3","article-title":"Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study","volume":"25","author":"Ercan","year":"2024","journal-title":"Lancet Oncol"},{"key":"2026080303135906000_bib45","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1200\/JCO.21.02583","article-title":"Temozolomide followed by combination with low-dose ipilimumab and nivolumab in patients with microsatellite-stable, O6-methylguanine-DNA methyltransferase-silenced metastatic colorectal cancer: the MAYA trial","volume":"40","author":"Morano","year":"2022","journal-title":"J Clin Oncol"},{"key":"2026080303135906000_bib46","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.ccell.2025.05.014","article-title":"Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models","volume":"43","author":"Vitiello","year":"2025","journal-title":"Cancer Cell"},{"key":"2026080303135906000_bib47","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.ccell.2025.05.010","article-title":"Induction of a mismatch repair deficient genotype by tailored chemical mutagenesis in experimental models of cancer","volume":"43","author":"Rousseau","year":"2025","journal-title":"Cancer Cell"},{"key":"2026080303135906000_bib48","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nbt.1523","article-title":"Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing","volume":"27","author":"Gnirke","year":"2009","journal-title":"Nat Biotechnol"},{"key":"2026080303135906000_bib49","doi-asserted-by":"crossref","first-page":"e000572","DOI":"10.1136\/esmoopen-2019-000572","article-title":"Whole exome sequencing analysis of urine trans-renal tumour DNA in metastatic colorectal cancer patients","volume":"4","author":"Crisafulli","year":"2019","journal-title":"ESMO Open"},{"key":"2026080303135906000_bib50","first-page":"91","article-title":"A genomic analysis workflow for colorectal cancer precision oncology","volume":"18","author":"Corti","year":"2019","journal-title":"Clin Colorectal Cancer"},{"key":"2026080303135906000_bib51","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1186\/s12864-019-6041-2","article-title":"SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events","volume":"20","author":"Bergstrom","year":"2019","journal-title":"BMC Genomics"},{"key":"2026080303135906000_bib52","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: the catalogue of somatic mutations in cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026080303135906000_bib53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13073-018-0539-0","article-title":"MutationalPatterns: comprehensive genome-wide analysis of mutational processes","volume":"10","author":"Blokzijl","year":"2018","journal-title":"Genome Med"},{"key":"2026080303135906000_bib54","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/978-1-0716-0810-4_28","article-title":"Bioinformatic methods to identify mutational signatures in cancer","volume":"2185","author":"Islam","year":"2021","journal-title":"Methods Mol Biol"},{"key":"2026080303135906000_bib55","doi-asserted-by":"crossref","first-page":"bbae249","DOI":"10.1093\/bib\/bbae249","article-title":"Mutational signatures of colorectal cancers according to distinct computational workflows","volume":"25","author":"Battuello","year":"2024","journal-title":"Brief Bioinform"},{"key":"2026080303135906000_bib56","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.3390\/cancers16172956","article-title":"Mutational signatures in colorectal cancer: translational insights, clinical applications, and limitations","volume":"16","author":"Crisafulli","year":"2024","journal-title":"Cancers (Basel)"},{"key":"2026080303135906000_bib57","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/laban.1257","article-title":"Design, analysis and reporting of tumor models","volume":"46","author":"Shaw","year":"2017","journal-title":"Lab Anim (NY)"},{"issue":"D1","key":"2026080303135906000_bib58","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","article-title":"The PRIDE database at 20 years: 2025 update","volume":"53","author":"Perez-Riverol","year":"2025  6","journal-title":"Nucleic Acids Res"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-26-0003\/3769734\/cd-26-0003.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-26-0003\/3803692\/cd-26-0003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/8\/1649\/3818110\/cd-26-0003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/8\/1649\/3818110\/cd-26-0003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:14:14Z","timestamp":1785741254000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/16\/8\/1649\/787119\/Pharmacologic-Inhibition-of-PMS2-Induces-MMR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":58,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4,21]]},"published-print":{"date-parts":[[2026,8,3]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-26-0003","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.33142929","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142908","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142914","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142926","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142905","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142917","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142932","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142911","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142896","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142923","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142902","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142935","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142899","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142920","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.33142893","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.8630706","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}