Phosphoprotein, protein kinase C, and second-messenger system changes in human multidrug-resistant cancer cells.

Abstract

Drug resistance in human cancer cells is one of the most, if not the most, important factors that prevents the successful treatment of cancer in patients. At the time of diagnosis, many tumors are not curable and often not responsive to cancer chemotherapy drugs. The majority of tumors, that are curable with chemotherapy, such as acute lymphocytic leukemia, Burkitt’s lymphoma, Hodgkin’s disease, choriocarcinoma, and aggressive lymphomas with diffuse histology, tend to occur in younger patients. The tumors that occur predominately in older patients, such as colorectal, lung, breast, and prostate, tend to be less responsive and less curable with chemotherapy alone. The etiology of these tumors is probably related to long-term carcinogen exposure, and this may explain the predominance in older patients. The mechanisms underlying this form of resistance are not completely understood, but work by Fairchild et al. [1] demonstrated remarkable similarities between the biochemical characteristics of de novo drug resistance in carcinogen-induced rat liver cancer cells and in multidrug-resistant human breast cancer cells. Thus, there may be similar mechanisms between carcinogen-induced drug resistance, which occurs more commonly in the elderly, and multidrug resistance that develops through exposure to anticancer drugs.