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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 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 |