Open Access

REVIEW

Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions

Matthew Rubinstein^1,*, Madeline Lauren Hong¹, Rishi Kumar Nanda¹, Daniel Thomas Jones¹, Hazem Aboaid², Yin Mon Myat³, Kyaw Zin Thein⁴

1 College of Osteopathic Medicine, Touro University, Henderson, NV 89014, USA
2 Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV 89106, USA
3 Department of Internal Medicine, One Brooklyn Health—Interfaith Medical Center Campus, Brooklyn, NY 11213, USA
4 Division of Hematology and Medical Oncology, Comprehensive Cancer Centers of Nevada, Central Valley, Las Vegas, NV 89169, USA

* Corresponding Author: Matthew Rubinstein. Email:

Oncology Research 2025, 33(11), 3161-3183. https://doi.org/10.32604/or.2025.067791

Received 13 May 2025; Accepted 19 August 2025; Issue published 22 October 2025

Abstract

The ever-expanding development of tissue-agnostic therapies which target malignancies based on specific mutations rather than tissue origin have transformed the landscape of oncology. The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. As the therapeutic arsenal continues to grow, it is crucial to understand how these therapies truly benefit patients and to address the barriers that stand in the way of making them more widely available. Although these therapies have shown effectiveness across multiple cancer types, substantial challenges persist, including overcoming the burden of intratumoral heterogeneity and resistance mechanisms that reduce therapeutic efficacy. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers.

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Keywords

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