Understanding the Promise and Challenges of Tumor-Agnostic Therapy: Could One Size Really Fit All?

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Tumor-agnostic therapies target molecular alterations, moving beyond traditional histology-based cancer treatments.
• Approved therapies target specific genomic alterations like NTRK/RET fusions, BRAF V600E mutations, and high tumor mutational burden (TMB-H).

Purpose of the Study:

• To review the variability in clinical outcomes for tumor-agnostic therapies across different cancer histologies.
• To examine the challenges and biological factors influencing response to these treatments.

Main Methods:

• Literature review of clinical outcomes and resistance mechanisms associated with tumor-agnostic therapies.
• Analysis of factors contributing to differential response rates in various cancer types.

Main Results:

• Tumor-agnostic therapies demonstrate clinical activity but response rates are not uniform across all cancers.
• Certain malignancies, like pancreatic and colorectal cancers, exhibit lower response rates due to intrinsic resistance mechanisms.

Conclusions:

• Tissue-specific resistance mechanisms, including bypass signaling and co-occurring alterations, impact treatment efficacy.
• Optimizing tumor-agnostic therapy use requires addressing biological complexities and refining drug development and clinical trial designs.