MDM4 amplification

Herein, we describe the case of a 59-year-old male with metastatic pancreatic ductal adenocarcinoma, referred to our center to receive immunotherapy (serplulimab, a novel anti-PD-1 antibody) combined with chemotherapy (gemcitabine/nab-paclitaxel). We investigated the potential mechanisms and reviewed the latest literature on predictive factors for HPD. These findings suggest that while chemotherapy combined with immunotherapy may hold promise for treating pancreatic cancer, it is imperative to identify and closely monitor patients with high-risk factors for HPD when using immunotherapy.

P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1b --> P1

Overall, while the pediatric and adult pHGG have similar outcomes, there are differences in their genomic structures, most notably in adult pHGG harboring a higher SCNA load. Overall, pHGG represent a biologically diverse set of clinically aggressive tumors that warrant further intensive study.

P1b, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Apr 2025 | Trial primary completion date: Jul 2023 --> Apr 2025

Human tumors that do not bear obvious TP53 genetic alterations but that phenocopy p53 activity loss are common, and the USP28 gene deletions are one likely cause.

P1b, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

This report shows that MDM4 amplification is an exceptional molecular event alternative to MDM2 amplification in ALT/WDLPS. This alteration should be considered and looked for in suspicious adipocytic tumors to optimize their surgical management.

In 592 GBM samples we found that 8.45% display MDM2 amplification. We suggest that patients with melanoma or GBM and amplifications in MDM2/4 and CDKN2A alterations may benefit from combinations of targeted inhibitors of MDM2/4 and CDK4/6, as well as immunotherapy.

NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.

MDM2 and MDM4 amplification are negative prognostic factors in TP53-WT breast cancer while MDM4 amp is associated with reduced survival in ICB-treated NSCLC.

Although amplification of MDM2/MDM4 was observed only in a small proportion of patients, it demonstrated an association with high TMB in several common cancer types. In addition, our data indicate that amplification of MDM2/MDM4 in different types of cancer is heterogeneous and that an appropriate immunotherapy strategy for patients with solid cancer should be noted.

Given the genomic similarities between melanoma and glioblastoma, we suggest that patients with melanoma or GBM and amplifications in MDM2/4 and CDKN2A deletions may need the development of combinations of targeted inhibitors of MDM2/4, CDK’s and immunotherapy. We are currently pursuing these translational directions.