The Contribution of Protein Kinase C to Multiple Drug Resistance in Cancer

Abstract

The use of combination chemotherapy in cancer treatment to address the heterogeneous nature of tumor cell populations has long been accepted as a standard practice. The acquisition of resistance to chemotherapeutic agents by malignant tumor cell populations during cancer therapy presents a formidable barrier to efforts underway to successfully manage the disease (Gottesman and Pastan, 1993). This has been the driving force behind the search for agents that can reverse clinical drug resistance in cancer therapy. In recent years, the heterogeneous nature of drug resistance mechanisms acquired by cancer cell populations during chemotherapy and innate in certain untreated cancers has become evident (Gottesman and Pastan, 1993; Fan et al., 1994; Kellen, 1994; Beck, 1989). For example, drug resistance mechanisms in cancer cell populations have been found to involve to various extents glutathione-S-transferases (Chapter 2), the multidrug resistance-associated protein (MRP) (Chapter 5), topoisomerases (Chapters 7 and 8), the oncogene Bcl-2 (Chapter 12), the drug-efflux pump P-glycoprotein (Endicott and Ling, 1989), and protein kinase C (PKC). This suggests that a combination of agents that antagonize distinct drug resistance mechanisms may be required to reverse clinical drug resistance in cancer and improve the ultimate therapeutic outcome for the patient.KeywordsPhorbol EsterDrug Resistance MechanismClinical Drug ResistanceDrug Efflux ActivityMurine Fibrosarcoma CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.