@Article{or.2026.083274,
AUTHOR = {Samuel Park, Julia Reitkopp, Rahul Patel, Justin Sigmund, Rishi Kumar Nanda, Kyaw Zin Thein},
TITLE = {Histology-Agnostic Drug Development in Thoracic and Head and Neck Cancers},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/27659},
ISSN = {1555-3906},
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.},
DOI = {10.32604/or.2026.083274}
}