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Personalizing Medicine in Head and Neck Squamous Cell Carcinoma: The Rationale for Combination Therapies.

ABSTRACT: Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Unfortunately, personalized medicine trials have had limited success in tumors that have complex combinations of disruptive genomic events, which drive differential responses to targeted therapies. Here, we will use head and neck squamous cell carcinoma as a model for genetically complex disease and discuss novel approaches to enhance personalized medicine trials for these complicated cases.

SUBMITTER: Birkeland AC

PROVIDER: S-EPMC4762450 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Personalizing Medicine in Head and Neck Squamous Cell Carcinoma: The Rationale for Combination Therapies.

Birkeland Andrew C AC Brenner J Chad JC

Medical research archives 20150101

Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Unfortunately, personalized medicine trials have had limited success in tumors that have complex combinations of disruptive genomic events, which drive differential responses to targeted therapies. Here, we will use head and neck squamous cell carcinoma as a model for genetically complex disease an ...[more]

PMID: 26913293

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Head and neck squamous cell carcinoma

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Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma.

Project description:Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice.

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Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma.

Project description:Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives.

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Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

Project description:Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainly manifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remained 50%, and it has not significantly improved in the past 10 years. Previous studies have shown that the tumor microenvironment (TME) plays a crucial role in the recurrence, metastasis, and drug resistance of patients with HNSCC. In this review, we summarize the role of anti-tumor and pro-tumor immune cells, as well as extracellular components in the TME of HNSCC. We also discuss classical HNSCC immunotherapy and highlight examples of clinical trials using CTLA-4 inhibitors and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1)-related combination therapies. We also outline some molecules in the TME known to regulate immunosuppressive cells. Furthermore, the role and underlying mechanism of radiation therapy on the TME, immune cells, and immune response are discussed.

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Genomics and advances towards precision medicine for head and neck squamous cell carcinoma.

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Osimertinib and dihydroartemisinin: a novel drug combination targeting head and neck squamous cell carcinoma.

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