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|Profile Name||MSH6 loss|
|Gene Variant Detail|
|Relevant Treatment Approaches|
|Molecular Profile||Indication/Tumor Type||Response Type||Relevant Treatment Approaches||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|MSH6 loss||colon cancer||no benefit||KU60648||Preclinical - Cell culture||Actionable||In a preclinical study, MSH6 deficient colon cancer cells did not respond to treatment with KU60648 in culture (PMID: 28224663).||28224663|
|MSH6 loss||colorectal cancer||predicted - sensitive||unspecified immune checkpoint inhibitor||Clinical Study - Cohort||Actionable||In a retrospective analysis, treatment with Keytruda (pembrolizumab), Opdivo (nivolumab), or the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with mismatch repair-deficient colorectal cancer harboring MSH6 loss or MSH2 and MSH6 loss versus patients with PMS2 loss or MLH1 and PMS2 loss resulted in a similar objective response rate (60.0% vs. 70.6% ), but led to greater progression-free survival (PFS) rates (1-year PFS 84.2% vs. 57.8%, 2-year PFS 78.2% vs. 54.2%) (PMID: 33631043).||33631043|
|MSH6 loss||colon carcinoma||not applicable||N/A||Preclinical||Emerging||Preclinical shRNA mediated-inhibition of PTEN-induced putative kinase 1 (PINK1) in colon carcinoma cells with MSH6 loss resulted in synthetic lethality, suggesting PINK1 may be a promising therapeutic target for MSH6 deficient cancer cells (PMID: 21242281).||21242281|
|Clinical Trial||Phase||Therapies||Title||Recruitment Status||Covered Countries||Other Countries|
|NCT02912559||Phase III||Atezolizumab + Fluorouracil + Leucovorin + Oxaliplatin Fluorouracil + Leucovorin + Oxaliplatin||Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair||Recruiting|
|NCT03911557||Phase II||Durvalumab + Tremelimumab||Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors||Recruiting|
|NCT04795661||Phase II||Pembrolizumab||Immunotherapy in MSI/dMMR Tumors in Perioperative Setting. (IMHOTEP)||Not yet recruiting|
|NCT02888743||Phase II||Durvalumab + Tremelimumab||Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer||Active, not recruiting|
|NCT04082572||Phase II||Pembrolizumab||Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers||Recruiting|