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The lancet oncology · Dec 2015
ReviewMolecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.
- Maria-Pia Bernardi, Samuel Y Ngan, Michael Michael, A Craig Lynch, Alexander G Heriot, Robert G Ramsay, and Wayne A Phillips.
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Surgery, St Vincent's Hospital, University of Melbourne, Victoria, Australia. Electronic address: mpbernardi16@gmail.com.
- Lancet Oncol. 2015 Dec 1;16(16):e611-21.
AbstractAnal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets.Copyright © 2015 Elsevier Ltd. All rights reserved.
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