In a significant stride toward combating oral cancer and its burdensome complications, researchers at the School of Dentistry at UT Health San Antonio have secured three substantial multi-year grants from the National Institutes of Health (NIH) totaling $6 million. This ambitious funding aims to catalyze advancements in both treatment modalities for oral squamous cell carcinoma (OSCC) and the management of debilitating symptoms such as oral mucositis and cancer-induced pain. These efforts hold promise for unveiling groundbreaking therapeutic options, potentially transforming the landscape of oral cancer care.
Oral squamous cell carcinoma, which originates in the epithelial lining of the mouth, remains a formidable challenge in oncology, constituting over 95% of oral cancer diagnoses. The incidence of OSCC is on an upward trajectory, with a troubling trend of late-stage diagnosis that yields a dismal 38% five-year survival rate. With approximately 200,000 individuals in the United States currently living with this malignancy and an annual death toll nearing 11,000, innovations in treatment are critically needed to improve patient outcomes and survival.
One pivotal area of research funded by a two-year, $315,000 grant focuses on the ion channel TRPC1 (Transient Receptor Potential Canonical 1). TRPC1 is known to regulate the flux of sodium and calcium ions across the cell membrane, influencing cellular processes vital for cancer cell survival and proliferation. Dr. Cara Gonzales and her team will investigate the effects of TRPC1 inhibition using sophisticated xenograft and syngeneic mouse models of OSCC. These models provide a controlled environment to study human cancer biology in vivo, allowing for precise evaluation of tumor response and immune system interactions when TRPC1 function is disrupted or pharmacologically blocked.
The innovative hypothesis driving this work postulates that selective inhibition of TRPC1 could induce apoptosis specifically in cancer cells without detrimentally affecting the immune cell populations that are essential for tumor surveillance and eradication. The outcome of this research could pave the way for novel targeted therapies that maximize cancer cell kill while minimizing immune suppression, an advancement that could significantly improve therapeutic windows and reduce side effects associated with current treatment regimens.
Beyond direct anti-cancer strategies, radiation-induced oral mucositis (RIOM) presents a severe clinical complication for patients receiving radiotherapy for head and neck cancers, including OSCC. RIOM is characterized by intense inflammation, ulcerations, and pain in the oral mucosa, often leading to treatment interruptions and substantial declines in quality of life. The pathophysiology of RIOM is complex, involving oxidative stress and inflammatory cascades that remain incompletely understood, thus hindering the development of effective preventative or therapeutic interventions.
A five-year, $3.1 million grant awarded to Drs. Shivani Ruparel and Brij B. Singh seeks to decipher the mechanistic role of the calcium-permeable ion channel TRPM2 (Transient Receptor Potential Melastatin 2) in the genesis of RIOM. TRPM2 is activated in response to oxidative stress and triggers inflammasome signaling pathways that regulate inflammatory responses. By unraveling how TRPM2-mediated immune activation contributes to the onset and progression of oral mucositis, the project aims to identify novel molecular targets for therapeutic intervention, potentially enabling strategies to mitigate mucositis severity and enhance patient tolerance to radiotherapy.
Managing the intense pain associated with oral cancer is another critical challenge that current opioid-based therapies inadequately address. Oral cancer pain is often refractory to conventional analgesics, with patients experiencing diminishing benefits over time due to tolerance and side effects. The underlying mechanisms contributing to oral cancer–associated pain are insufficiently characterized, impeding the discovery of new analgesic targets.
One of the three grants, totaling $2.6 million over four years under the leadership of Dr. Ruparel, targets the truncated isoform of the Tyrosine Kinase B receptor, TrkBT1. This receptor variant is highly expressed in oral cancers and has been implicated in neuropathic pain pathways. The research will explore TrkBT1’s dual role in modulating nociceptive signaling in sensory neurons and influencing tumor microenvironment interactions that may exacerbate pain and tumor progression. Understanding these dynamics is anticipated to foster the development of innovative, mechanism-based pain therapies that not only improve analgesia but may also impact tumor growth.
The multidisciplinary approach of these projects is reinforced by the collaboration across three specialized centers within the dental school: the Center for Regenerative Sciences, the Center for Pain Therapeutics and Addiction Research, and a combined effort involving both centers. This environment nurtures translational research, integrating laboratory discoveries with clinical implications, and accelerates the journey from bench to bedside.
Each of these grants not only embodies a significant financial investment but also represents a concerted effort to fill critical knowledge gaps in the biology and treatment of oral cancer and its complications. Collectively, the research aims to yield transformative therapeutic options that address the multifaceted nature of oral cancer — from tumor eradication to mitigation of treatment side effects and pain management. The breakthroughs anticipated from these investigations have the potential to vastly improve survival rates and quality of life for patients suffering from this devastating disease.
UT Health San Antonio, as the academic health center of The University of Texas at San Antonio, is uniquely positioned to lead these efforts through its extensive infrastructure and clinical expertise. The School of Dentistry, ranked as the top dental school in Texas, combines cutting-edge research initiatives with comprehensive education and community care, emphasizing the integration of scientific innovation and patient-centered treatment.
In the continuous battle against oral cancer, these NIH-funded endeavors illuminate promising new avenues and underscore the essential role of rigorous scientific inquiry in addressing one of the most challenging malignancies in head and neck oncology. The coming years are poised to witness significant progress, unlocking novel treatment paradigms that may redefine the prognostic landscape and improve countless lives.
Subject of Research: Oral Cancer Treatment and Pain Management
Article Title: (Not provided)
News Publication Date: November 7, 2025
Web References:
– TRPC1 Targeting Grant: https://reporter.nih.gov/search/i5XkB_iDZEe1kU16DkIKow/project-details/11158285
– TRPM2 in Oral Mucositis Grant: https://reporter.nih.gov/search/-gZqooB-KU-NI-IK2vwhnQ/project-details/11234576
– TrkBT1 Isoform in Cancer Pain Grant: https://reporter.nih.gov/search/qNeu_ttndEmPuxjgmg45sg/project-details/11139335
Keywords: Oral cancer, oral squamous cell carcinoma, TRPC1, TRPM2, oral mucositis, radiation-induced mucositis, cancer pain, TrkBT1, ion channels, inflammation, inflammasome, pain management
