Molecular Profile Detail

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Profile Name MSH6 loss
Gene Variant Detail

MSH6 loss (loss of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
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 USA | CAN 0
NCT04082572 Phase II Pembrolizumab Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers Unknown status USA 0
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 USA 1
NCT03911557 Phase II Durvalumab + Tremelimumab Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors Recruiting USA 0