Transient receptor potential (TRP) cation channel superfamily plays critical roles in variety of processes, including temperature perception, pain transduction, vasorelaxation, male fertility, and tumorigenesis. One of seven families within the TRP superfamily of ion channels, the melastatin, or TRPM family comprises a group of eight structurally and functionally diverse channels. Of all the members of TRPM subfamily, TRPM8 is the most notable one. A lot of literatures have demonstrated that transient receptor potential melastatin 8 (TRPM8) could perform a myriad of functions in vertebrates and invertebrates alike. In addition to its well-known function in cold sensation, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Recent studies have shown that TRPM8 is necessary to the initiation and progression of tumors, and the aberrant expression of TRPM8 was found in varieties of tumors, such as prostate tumor, melanoma, breast adenocarcinoma, bladder cancer, and colorectal cancer, making it a novel molecular target potentially useful in the diagnosis and treatment of cancer. This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy.

TRPM8: a potential target for cancer treatment

Gastrointestinal stromal tumors (GISTs) are most frequent mesenchimal neoplasms of the gastrointestinal tract. Current knowledge demonstrates that the KIT and PDGFRA gene mutations play a central part in the pathogenesis. Mutations can be subdivided into primary and secondary mutations. Secondary mutations usually occur in KIT kinase domains after tyrosine kinase inhibitors treatment resulting in resistance to drugs. Besides surgery, therapy with tyrosine kinase inhibitors has led to develop novel treatments for patients now. However, secondary resistance has become a significant concern, illustrating the need to increase collaboration between surgical management and molecular therapy.

Gastrointestinal Stromal Tumors Short Review on KIT/PDGFRA Gene Mutations and Molecular Therapy

Targeted therapy based on the inhibition of the receptor tyrosine kinases has improved the outcome of patients with metastatic, recurrent and/or unresectable gastrointestinal stromal tumors (GIST). Activating mutations of KITand PDGFRA genes, which code for receptor tyrosine kinases, play an important role in the malignant transformation of stromal cells in the gastrointestinal tract. The response to targeted therapy is associated with the presence and type of mutations. Molecular identification of the primary mutational status became an important tool in predicting the response to therapy (sensibility/resistance). The identification of secondary mutations occurring in patients treated with targeted therapy may explain the cause of acquired, secondary resistance of GIST. In these cases, mutational analysis represents a tool to explain failure of the therapy and provides a rationale for alternative therapeutic strategies.

Augustináková A

Papers

Gastrointestinal stromal tumor molecular diagnostics in relation to the prediction of a therapeutic response to targeted biological therapy