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Updated: Jul 5, 2025
Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting
Published on: September 25, 2012
Impact of tissue-agnostic approvals on management of primary brain tumors
Manmeet S Ahluwalia1, Atulya A Khosla2, Ahmad Ozair3
1Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA; Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
Abstract:
Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses. We describe current and potential impact of tissue-agnostic approvals on management of PBTs. We discuss data from clinical trials for PBTs regarding tissue-agnostic targets, including BRAFV600E, neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability-high (MSI-High), mismatch repair deficiency (dMMR), and high tumor mutational burden (TMB-H), in context of challenges in managing PBTs. Described are additional tissue-agnostic targets that hold promise for benefiting patients with PBTs, including RET fusion, fibroblast growth factor receptor (FGFR), ERBB2/HER2, and KRASG12C, and TP53Y220C.
Insights
Tissue-agnostic therapies show promise for rare primary brain tumors (PBTs). Further research is needed to integrate these novel treatments into routine PBT care, addressing limited options and poor prognoses.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Novel tissue-agnostic therapeutics targeting specific genetic alterations have gained FDA approval, demonstrating efficacy across various cancer types.
- Primary brain tumors (PBTs) are rare, leading to limited representation in early clinical trials for these targeted therapies.
- PBTs present unique management challenges due to their diversity, limited treatment options, and generally poor prognoses.
Purpose of the Study:
- To review the current and potential impact of tissue-agnostic drug approvals on the management of primary brain tumors.
- To discuss existing and emerging tissue-agnostic targets relevant to PBTs within the context of clinical trial data.
Main Methods:
- Review of FDA-approved tissue-agnostic therapeutics and relevant basket trial data.
- Analysis of clinical trial outcomes for PBTs incorporating tissue-agnostic targets.
- Identification of additional promising tissue-agnostic targets for PBTs.
Main Results:
- Established tissue-agnostic targets in PBTs include BRAFV600E, neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability-high (MSI-High), mismatch repair deficiency (dMMR), and high tumor mutational burden (TMB-H).
- Emerging targets with potential benefit for PBT patients include RET fusion, fibroblast growth factor receptor (FGFR), ERBB2/HER2, KRASG12C, and TP53Y220C.
Conclusions:
- Tissue-agnostic therapies represent a significant advancement in oncology, with growing relevance for primary brain tumors.
- Further research and clinical trial inclusion are crucial to optimize the use of these targeted treatments for PBTs, potentially improving patient outcomes.
