A team led by Yong Teng, PhD, a researcher with Winship Cancer Institute of Emory University’s Cell and Molecular Biology Research Program and associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, conducted a noteworthy study that could impact future treatment of squamous cell head and neck cancer.
The research, published recently in Science Advances, delves into the effects of inhibiting heat shock protein 90 (HSP90), a molecular chaperone protein, using ganetespib, a type of synthetic drug called a small-molecule inhibitor. Through a combination of clinical insights and animal studies, Teng and the team of researchers explored the potential impact of HSP90 inhibition on tumor metabolism and immune response, particularly in the context of radiotherapy.
Teng explains, “These findings provide a molecular basis for exploring the synergy of HSP90 inhibitors with radiotherapy and offer potential avenues for improving outcomes” in patients with squamous cell head and neck cancer.
Teng’s research challenged conventional approaches to cancer treatment by proposing a novel strategy that combines HSP90 inhibition with radiotherapy. By uncovering the molecular mechanisms underlying this approach, the research provides a compelling rationale for exploring combination therapies to improve outcomes in patients with squamous cell head and neck cancer.
Ganetespib, acting as an HSP90 inhibitor, emerges as a pivotal player in disrupting glycolysis within head and neck cancer cells. By targeting key enzymes involved in glycolysis, namely PFKP and PKM2, the drug effectively stifles the metabolic pathways essential for cancer cell survival and proliferation. Reducing tumor sugar metabolism using ganetespib helps immune cells enter tumors more easily by decreasing a signaling molecule called interleukin-8, which relies on sugar metabolism. Essentially, ganetespib makes cancer cells more sensitive to radiation treatment by reducing their sugar metabolism increase caused by radiation. It also strengthens the body's immune response against tumors by enhancing the activity of T cells, which attack cancer cells. Combining ganetespib with radiation therapy results in a stronger anti-cancer effect compared to using either treatment alone.
“The rationale for this study is based on clinical observations derived from a single-arm Phase II exploratory study (Winship2572-13, NCT02334319) led by Dr. Nabil Saba,” said Teng. He and Saba have previously collaborated on several completed and ongoing clinical and basic research studies. This prior collaboration also resulted in a Nature Medicine paper in 2023 and a JAMA Oncology paper this year.
Looking ahead, the researchers envision further investigations into the clinical application of HSP90 inhibitors alongside other immune-based therapies. This collaborative effort aims to refine cancer treatment strategies and translate scientific discoveries into tangible benefits for patients.
Teng underscores the potential benefits of these findings, highlighting the prospect of enhancing treatment outcomes for patients with squamous cell head and neck cancer. Drawing inspiration from early clinical trials of ganetespib, the study emphasizes the importance of rational combination therapies in maximizing therapeutic efficacy.
Ultimately, this research instills hope for patients with squamous cell head and neck cancer by offering a promising avenue for enhancing the effectiveness of immunotherapy in cancer treatment. By exploring the intricate interplay between tumor metabolism, immune response and therapeutic interventions, the study paves the way for innovative approaches that hold the promise of transforming the landscape of cancer care.
The collaborative efforts of researchers from Winship Cancer Institute of Emory University and other institutions shed light on a promising therapeutic strategy that could significantly impact the management of squamous cell head and neck cancer. With further exploration and clinical validation, this novel approach has the potential to improve treatment outcomes and offer new hope to patients living with this challenging disease.