Chemokine-cytokine networks in the head and neck tumor microenvironment

Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.This study was supported by Ramalingaswami Fellowship (Grant number: D.O.NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi to Muzafar A. Macha. Sidra Medicine Precision Program funded this research to Mohammad Haris (5081012001, 5081012001) and Ajaz A. Bhat (5081012003)

Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents

Cancer is one of the leading causes of death and significantly burdens the healthcare system. Due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. The use of natural products as anticancer agents is an acceptable therapeutic approach due to accessibility, applicability, and reduced cytotoxicity. Natural products have been an incomparable source of anticancer drugs in the modern era of drug discovery. Along with their derivatives and analogs, natural products play a major role in cancer treatment by modulating the cancer microenvironment and different signaling pathways. These compounds are effective against several signaling pathways, mainly cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch pathway, Wnt pathway, and Hedgehog pathway). The historical record of natural products is strong, but there is a need to investigate the current role of natural products in the discovery and development of cancer drugs and determine the possibility of natural products being an important source of future therapeutic agents. Many target-specific anticancer drugs failed to provide successful results, which accounts for a need to investigate natural products with multi-target characteristics to achieve better outcomes. The potential of natural products to be promising novel compounds for cancer treatment makes them an important area of research. This review explores the significance of natural products in inhibiting the various signaling pathways that serve as drivers of carcinogenesis and thus pave the way for developing and discovering anticancer drugs.This study was supported by Sidra Medicine Precision Program funding to Ajaz A. Bhat (5081012003) and Mohammad Haris (5081012002)

Exploring Dysregulated Signaling Pathways in Cancer.

Cancer cell biology takes advantage of identifying diverse cellular signaling pathways that are disrupted in cancer. Signaling pathways are an important means of communication from the exterior of cell to intracellular mediators, as well as intracellular interactions that govern diverse cellular processes. Oncogenic mutations or abnormal expression of signaling components disrupt the regulatory networks that govern cell function, thus enabling tumor cells to undergo dysregulated mitogenesis, to resist apoptosis, and to promote invasion to neighboring tissues. Unraveling of dysregulated signaling pathways may advance the understanding of tumor pathophysiology and lead to the improvement of targeted tumor therapy. In this review article, different signaling pathways and how their dysregulation contributes to the development of tumors have been discussed