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Tachykinins and their Receptors in Human Malignancies

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The possibility of links between phsychosocial factors and cancer incidence and progression has generated considerable scientific and public interest. Tachykinins, including substance P, neurokinin A and B, hemokinin-1 and endokinins, are a family of neuropeptides, acting through three types of transmembrane G-protein coupled receptors denoted NK1, NK2 and NK3. Besides, their role as neurotransmitters in peripheral and central nervous system, tachykinins and their receptors are also expressed in several non neuronal cells contributing to the fine connections between nervous systems and peripheral organ system such as, respiratory, cardiovascular, immune, endocrine, gastrointestinal and genitourinary. Being so much involved in regulating physiological functions, they, of course, can concur to pathological conditions including cancer.

Tachykinins can act on different steps of carcinogenesis. Tumors expressing NK receptors, such as astrocytoma, glioma, neuroblastoma, pancreatic cancer and melanoma, can misuse tachykinin-induced signaling, operating in normal cells, to promote proliferation and survival of cancer cells and to release cytokines and soluble mediators favoring tumor growth. In neuroblastoma, breast and prostate carcinomas tachykinins facilitate tumor metastatic infiltration in the bone marrow. In neuroendocrine carcinoma, tachykinins are responsible of symptoms associated with these pathologies including flushing, diarrhea, wheezing and right heart disease. In addition, regardless tumor histology, tachykinins may favor cancer incidence and metastatic progression by influencing blood flux and neovascularization in tumor formation as well as inducing immunesuppression mediated by neurogenic inflammation due to stress or surgery.

However, the precise involvement of tachykinins in cancer pathologies and the potentiality to become effective pharmacological drug targets remain to be fully defined.

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Keywords: NK receptors; Tachykinins; astrocytoma/glioma; carcinoma; leukemia; metastasis; neuroblastoma; pancreatic cancer

Document Type: Research Article

Affiliations: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299 00161 Rome, Italy.

Publication date: 2006-08-01

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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