MLH1 (MutL homolog 1)

P=N/A, N=77, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

She started combination therapy with ipilimumab and nivolumab, achieving complete metabolic and imaging response as confirmed by PET-CT at 12 months...She started treatment with pembrolizumab, achieving a sustained complete response at 12 months...Both cases illustrate the remarkable clinical benefit of immunotherapy in patients with early peritoneal recurrence of MSI-H/dMMR colon cancer, which is usually associated with poor prognosis. These cases highlight the need to consider the molecular profile in therapeutic planning and reinforce the emerging value of immunotherapy as a cornerstone in the management of these cases.

MSI testing which has been used historically to identify patients with Lynch Syndrome and evaluate the severity and prognosis of MSI carcinomas now plays an important role in identifying patients who will benefit from targetable therapy. MMR study therefore recommended in all cases of endometrial carcinomas and detection of MMR proteins by IHC can indirectly reflect the status of MSI and is a reliable method of MSI detection.

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P2, N=128, Not yet recruiting, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Clones were injected subcutaneously or intracranially with or without anti-PD-1/anti-CTLA4 and dexamethasone...Rather, rejection depended on increased secretion of pro-inflammatory chemokines. Msh2 and Mlh1 loss was not equivalent, suggesting that additional studies are needed to elucidate germline and somatic mismatch repair gene-specific immune alterations.

This case highlights that lung adenocarcinoma can be a manifestation of LS and underscores the critical importance of retrospective MMR testing in establishing the diagnosis. Furthermore, it demonstrates the efficacy of immune checkpoint inhibitions in advanced dMMR tumors.

An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=20 --> 0 | Trial completion date: Sep 2032 --> Jan 2026 | Initiation date: Apr 2026 --> Oct 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Sep 2030 --> Jan 2026

P=N/A, N=20000, Recruiting, Arbor Research Collaborative for Health | N=10000 --> 20000

This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.