Open Access
REVIEW
Histology-Agnostic Drug Development in Thoracic and Head and Neck Cancers
Samuel Park1,*, Julia Reitkopp1, Rahul Patel1, Justin Sigmund1, Rishi Kumar Nanda1, Kyaw Zin Thein1,2
1 College of Osteopathic Medicine, Touro University, Henderson, NV, USA
2 Division of Hematology and Medical Oncology, Comprehensive Cancer Centers of Nevada, Central Valley, Las Vegas, NV, USA
* Corresponding Author: Samuel Park. Email: 
(This article belongs to the Special Issue: Advances in Cancer Therapeutics)
Oncology Research https://doi.org/10.32604/or.2026.083274
Received 31 March 2026; Accepted 29 June 2026; Published online 23 July 2026
Abstract
Recent advancements in oncology have led to the development of histology-agnostic therapies that target genetic alterations regardless of the tumor’s tissue of origin. We focus on key approved therapies, including pembrolizumab, dostarlimab, larotrectinib, entrectinib, dabrafenib plus trametinib, selpercatinib, pralsetinib, and trastuzumab deruxtecan. A detailed analysis of pivotal trial data was conducted to elucidate the specific enrollment, efficacy, and outcomes for non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and head and neck squamous cell carcinomas (HNSCC) within these broader basket trials. The review further explores challenges unique to these histologies, such as the discordance of Tumor Mutational Burden (TMB) as a biomarker in lung cancer versus its agnostic approval, and the transformative potential of Human Epidermal Growth Factor Receptor 2 (HER2)-targeted agents in salivary gland tumors. While these therapies have demonstrated efficacy across various solid tumors, significant hurdles remain, including limited patient representation in trials and the need for comprehensive next-generation sequencing (NGS) to identify rare alterations. We propose considerations for better integrating these therapies into standard-of-care algorithms and utilizing emerging biomarkers to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers in Thoracic and Head and Neck cancers. This review aims to provide a comprehensive update on the current state of histology-agnostic drug development, with a focus on its application in Thoracic and Head and Neck malignancies.
Keywords
Tissue-agnostic drugs; advances in cancer therapeutics; precision oncology updates; thoracic cancers; head and neck cancers
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