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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04082572 Phase II Pembrolizumab Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers Recruiting USA 0
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
NCT03911557 Phase II Durvalumab + Tremelimumab Durvalumab and Tremelimumab Combination in Somatically Hypermutated Recurrent Solid Tumors Recruiting 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 | DEU 1