If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Tumor-agnostic US Food and Drug Administration (FDA) approvals are revolutionizing cancer treatment by targeting specific molecular alterations rather than tumor location.
• This approach has demonstrated remarkable response rates and expanded drug access for patients with rare or ultra-rare malignancies.

Purpose of the Study:

• To review the current landscape of tumor-agnostic approvals in oncology.
• To highlight the biological rationale and clinical benefits of this genomically driven approach.
• To propose the expansion of future tissue-agnostic studies to include both solid and hematologic cancers.

Main Methods:

• Review of existing US FDA-approved tumor-agnostic therapies and their corresponding molecular targets (e.g., NTRK fusions, BRAF mutations, microsatellite instability).
• Analysis of the biological basis for targeting common molecular abnormalities across different cancer types.
• Identification of shared druggable targets in solid and hematologic malignancies.

Main Results:

• Several tumor-agnostic therapies are approved, including larotrectinib/entrectinib/repotrectinib, selpercatinib, dabrafenib/trametinib, pembrolizumab/dostarlimab, and trastuzumab deruxtecan.
• Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms.
• Identical driver molecular abnormalities (e.g., BRAF V600E, NTRK fusions, PD-L1 amplification) are found in both solid and hematologic cancers and are responsive to targeted therapies.

Conclusions:

• The tumor-agnostic, genomically driven approach is highly effective and addresses unmet needs in oncology.
• There is a strong rationale for including both solid and hematologic cancers in future biomarker-based, tissue-agnostic basket studies and approvals.
• Bridging the divide between solid and hematologic malignancies through tissue-agnostic therapies will further enhance precision oncology.