12/25/2025
This , we’re recognizing D**g Ren, MD, PhD, recipient of the 2025 MRF Resident/Fellow Award at The Regents of the University of California, Irvine, his research is funded in honor of Richard Draeger.
Dr. Ren shares more about his work, "Molecular Investigation of Metastatic Sinonasal Mucosal Melanoma":
Sinonasal mucosal melanoma (SNMM) is a rare primary malignancy with aggressive clinical behavior, affecting the sinonasal tract. The overall incidence of SNMM has been estimated at 0.5 to 0.71/million people per year, accounting for < 2% of all malignant melanomas and approximately 4% of head and neck melanomas. It is commonly seen in elderly patients, ranging from 13 to 93 years of age, with a median age of 66 years, and shows a slight female predilection. Since SNMM patients are often diagnosed at an advanced stage and exhibits aggressive clinical behavior, the prognosis is extremely poor, with a recurrence rate of over 50% and a 5-year survival rate of less than 30%. Wide surgical excision with negative margins is generally considered the first-line treatment for SNMM patients, with postoperative radiation therapy often used to improve locoregional control. Despite the increasing availability of systemic therapy strategies for the treatment of SNMM patients, they have demonstrated little or no survival benefit. Distant metastases, most commonly involving the lungs, brain, bones, liver, and lymph nodes, significantly contribute to the mortality of SNMM patients, with liver being the most common metastatic site. The 5-year overall survival rate for SNMM patients with lymph node metastasis was 5.3%, compared to 35.2% for patients without lymph node metastasis. Notably, SNMM presents with a high metastatic potential, ranging from 12% to 66%. Given the high metastatic rate of SNMM and its dismal prognosis, it is of paramount importance to investigate potential diagnostic biomarkers for the early detection of SNMM with distant metastasis (SNMM-M) and identify therapeutic targets for individualized treatment. Using both DNA and RNA next-generation sequencing, we discovered that SNMM-M harbors unique molecular profiles: structure-specific endonuclease subunit (SLX4) was only detected in SNMM-M. A comparative analysis of genomic alterations and copy number variations of clinically actionable genes between SNMM-M and SNMM without distant metastasis (SNMM-nM) revealed that CDK4 gains/amplifications that can be targeted by Palbociclib (a selective CDK4/6 inhibitor) were commonly seen in SNMM-M cases, while alterations of receptor tyrosine kinase gene targeted by tyrosine kinase inhibitors (TKIs) and homologous recombination repair gene targeted by PARP inhibitors were highly enriched in SNMM-nM cases. Additionally, PD-L1 targeted by immune checkpoint inhibitor was more commonly expressed in SNMM-nM. These exploratory findings suggest that SLX4 mutation may serve as a potential prognostic biomarker and that CDK4 inhibitors could represent promising therapeutic options for SNMM-M. In contrast, immunotherapy, TKIs and PARP inhibitors are appropriate therapeutic strategist for SNMM-nM patients.
Learn more here: https://buff.ly/u0SGvBm
