Abstract

RECENT NEWER ADVANCEMENT IN CANCER CHEMOTHERAPY

Upasana Khatri, Bhuvanesh Baniya* and Sunil Saini

ABSTRACT

Carcinogens activate and chemopreventive agents suppress NF-κB activation, a major mediator of inflammation. First, inflammatory markers such as cytokines (such as TNF, IL-1, IL-6, and chemokines), enzymes (such as COX-2, 5-LOX, and matrix metalloproteinase-9 [MMP-9]), and adhesion molecules (such as intercellular adhesion molecule 1, endothelium leukocyte adhesion molecule 1, and vascular cell adhesion molecule 1) have been closely linked with tumorigenesis. Second, All of these inflammatory gene products have been shown to be regulated by the nuclear transcription factor, NF-κB. Third, NF-κB has been shown to control the expression of other gene products linked with tumorigenesis such as tumor cell survival or antiapoptosis (Bcl-2, BclxL,IAP-1, IAP-2, XIAP, survivin, cFLIP, and TRAF-1), proliferation (such as c-myc and cyclin D1), invasion (MMP-9), and angiogenesis (vascular endothelial growth factor). Fourth, in most cancers, chronic inflammation precedes tumorigenesis. Fifth, most carcinogens and other risk factors for cancer, including cigarette smoke, obesity, alcohol, hyperglycemia, infectious agents, sunlight, stress, food carcinogens, and environmental pollutants, have been shown to activate NF-κB. Sixth, constitutive NF-κB activation has been encountered in most types of cancers. Seventh, most chemotherapeutic agents and γ-radiation, used for the treatment of cancers, lead to activation of NF-κB. Eighth, activation of NF-κB has been linked with chemoresistance and radioresistance. Ninth, suppression of NF-κB inhibits the proliferation of tumors, leads to apoptosis, inhibits invasion, and suppresses angiogenesis. Tenth, polymorphisms of TNF, IL-1, IL-6, and cyclin D1 genes encountered in various cancers are all regulated by NF-κB. Also, mutations in genes encoding for inhibitors of NF-κB have been found in certain cancers. Eleventh, almost all chemopreventive agents described above have been shown to suppress NF-κB activation.

Keywords: Kyprolis, Regorafenib, Revlimid, Gilotrif, Pomalyst, Imbruvica.