Miami Cancer Institute

Miami Cancer Institute Researchers Identify New Gene Signature for Glioblastoma

June 5, 2024

RNA sequencing of patients in a Phase 2 trial pinpoints hyperactivated DNA damage response gene signature as a biomarker

 

MIAMI, FL - June 5, 2024 - Researchers from Miami Cancer Institute, part of Baptist Health South Florida, have identified a new gene signature for glioblastoma through integrating genomics and transcriptomics. The study, titled “Base Excision Repair Inhibitor TRC102 and Temozolomide for Recurrent Glioblastoma (BERT): A Multicenter, Phase 2, Adult Brain Tumor Consortium Trial”, was published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

 

“Glioblastoma is an aggressive and lethal brain tumor. Nearly all patients experience tumor recurrence once conventional treatment strategies fail,” said Manmeet S. Ahluwalia, M.D., MBA, FASCO, Fernandez Family Foundation Endowed Chair in Cancer Research, Chief of Medical Oncology, Chief Scientific Officer, and Deputy Director at Miami Cancer Institute, and the first author and the principal investigator of the study which originated at Cleveland Clinic. “This trial has demonstrated a potential for better patient selection for therapeutic targeting using a hyperactivated DNA damage response signature.”

 

In this multicenter Phase 2 conducted through the National Cancer Institute (NCI) Adult Brain Tumor Consortium, adults with glioblastoma at first recurrence received a DNA alkylating agent (temozolomide) combined with a DNA base excision repair inhibitor (TRC102). The combination therapy was found to be safe and feasible for further evaluation in biomarker-enriched trials. A subset of patients benefiting from combination therapy was identified, termed “extended survivors.” RNA sequencing of tumor tissue collected at diagnosis demonstrated significant enrichment for gene signatures of DNA damage response (DDR), chromosomal instability (CIN70, CIN25), and cellular proliferation (PCNA25) in these “extended survivors.”

 

“Through genomic analyses, we also gained insights into the context of tumor vulnerability to DNA damage,” said Ahmad Ozair, M.D., second author of the study. “The DDR signature was found to be present in nearly 10 percent of patients in The Cancer Genome Atlas database, indicating the utility of identifying responder subsets.

Building on these promising findings, a biomarker-enriched trial in newly diagnosed glioblastoma patients is planned. Click here to read the full study here.

About Miami Cancer Institute

Miami Cancer Institute brings to South Florida access to personalized clinical treatments and comprehensive support services delivered with unparalleled compassion. No other cancer program in the region has the combination of cancer-fighting expertise and advanced technology—including the first proton therapy center in South Florida, Latin America and the Caribbean, and one of the only radiation oncology programs in the world with each of the newest radiation therapies in one place—to diagnose and deliver precise cancer treatments that achieve the best outcomes and improve the lives of cancer patients. The Institute offers an impressive roster of established community oncologists and renowned experts, clinical researchers and genomic scientists recruited from the nation’s top cancer centers. Selected as Florida’s only member of the Memorial Sloan Kettering Cancer (MSK) Alliance, Miami Cancer Institute is part of a meaningful clinical collaboration that affords patients in South Florida access to innovative treatments and ensures that the standards of care developed by their multidisciplinary disease management teams match those at MSK. For more information, please visit https://cancer.baptisthealth.net/miami-cancer-institute.

Miami Cancer Institute is part of Baptist Health Cancer Care, the largest cancer program in South Florida, with locations from the Florida Keys to the Palm Beaches.

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