Adenoid cystic carcinoma (ACC) of the head and neck, although rare, poses significant challenges due to its potential for local recurrence and metastasis. Despite being generally slow-growing, ACC often lacks effective treatment options, especially for recurrent or metastatic cases. Recently, a team of researchers led by Dr. Yoshihito Kano with the contribution of Dr. Takahiro Naito from Tokyo Medical and Dental University explored the efficacy of immunotherapy, particularly immune checkpoint inhibitors (ICIs), and the utility of comprehensive genomic profiling (CGP) in managing this formidable disease. Their findings, published in the journal Medicina, illuminate the potential role of ICIs and the importance of identifying biomarkers for personalized treatment in ACC.
Dr. Kano and his colleagues from TMDU examined a nationwide database comprising hundreds of cases of ACC of the head and neck. This study is one of the most extensive analyses of its kind, offering insights into the real-world application of ICIs in ACC patients. The results revealed that while ICIs showed promise, their efficacy was limited, with a modest objective response rate (ORR) and about half of the patients experiencing disease control. These figures highlight the need for more refined biomarkers to predict which patients might benefit most from ICI therapy.
The team also analyzed the tumor mutational burden (TMB), a factor often associated with a better response to ICIs in other cancers. However, in the case of ACC, the TMB was found to be relatively low, which may explain the limited effectiveness of ICIs in this population. Interestingly, some patients with specific genetic alterations, such as MYB structural variants, responded better to ICIs, suggesting that these variants could serve as potential predictive biomarkers for immunotherapy in ACC.
Dr. Kano emphasized the significance of these findings, noting, “Our study underscores the importance of comprehensive genomic profiling in identifying potential biomarkers that could predict the response to immunotherapy in ACC patients. While the overall response to ICIs in ACC is modest, certain genetic profiles, such as MYB variants, may offer a glimmer of hope for more effective treatment strategies.”
In their detailed analysis, the researchers identified several commonly mutated genes in ACC patients, including NOTCH1, KDM6A, and MYB. Among these, the MYB structural variant emerged as a particularly interesting candidate for further investigation. The study reported that patients with MYB structural variants had a more favorable response to ICIs.
One case that stands out involved a 63-year-old male patient with a submandibular gland tumor who exhibited a prolonged stable disease following treatment with pembrolizumab, an ICI. This patient had a MYB structural variant along with other mutations, yet managed to maintain a response to the therapy for over a year and a half. This case highlights the potential of MYB as a biomarker for selecting patients who may benefit from immunotherapy.
The study also pointed to the challenges of treating ACC with ICIs due to the tumor’s molecular and histological characteristics, such as lower immunogenicity and fewer tumor-infiltrating lymphocytes. These factors contribute to the limited efficacy of ICIs in ACC, despite their success in other types of head and neck cancers. Nevertheless, the team remains optimistic about the future of personalized medicine in ACC treatment, advocating for further studies to validate these findings and explore new therapeutic avenues.
In conclusion, this comprehensive analysis by Dr. Kano and his team represents a significant step forward in understanding the role of immunotherapy in treating ACC of the head and neck. The identification of MYB structural variants as a potential biomarker offers a new direction for personalized treatment strategies, bringing hope to patients who have few options. As the field of precision medicine continues to evolve, such research will be crucial in developing more effective treatments for rare and challenging cancers like ACC.
Journal Reference
Naito, T., Noji, R., Kugimoto, T., Kuroshima, T., Tomioka, H., Fujiwara, S., Suenaga, M., Harada, H., & Kano, Y. (2023). The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck. Medicina, 59, 2111. DOI: https://doi.org/10.3390/medicina59122111
About the Authors
Dr. Yoshihito Kano is a distinguished Junior Associate Professor at Tokyo Medical and Dental University (TMDU), where he specializes in medical oncology, cancer genomic medicine, and targeted therapy. Dr. Kano’s academic journey began at TMDU, where he earned his medical degree in 2005. He furthered his education at the same institution, completing his Doctor’s Course in the Division of Medical Sciences in 2012.
In addition to his roles at TMDU, Dr. Kano has an impressive external career. He spent five years as a Postdoctoral Fellow at the University of Toronto, Department of Laboratory Medicine and Pathobiology, from 2014 to 2019. This international experience enriched his research and clinical skills, particularly in genome biology, tumor diagnostics and therapeutics, tumor biology, gastroenterology, and general internal medicine. His expertise in KRAS biology and targeted therapy is underscored by his significant contributions to the field, as evidenced by his publications in prestigious journals such as Nature Communications, PNAS, and Cancer Research.
Dr. Kano’s contributions to the field of oncology are underscored by his commitment to advancing cancer genomic medicine and developing targeted therapies. His work continues to impact the medical community, both in Japan and internationally, as he leads innovative research and provides comprehensive patient care.
Dr. Takahiro Naito is a dedicated dentist (DDS) specializing in oral and maxillofacial surgery. Currently, he is a PhD student at Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, focusing on Health Sciences and Biomedical Engineering. Since April 2021, he has been actively involved in a comprehensive genetic analysis project on oral cancer. His research aims to advance the understanding and treatment of oral cancer through detailed genomic studies.
