Platinum compounds are the most effective drugs in the fight against
ovarian cancer. Unfortunately, many ovarian
tumors are not eradicated by
chemotherapy due to the emergence of
drug-resistant clones during
therapy, and hence 5-year survival rate of women afflicted with this disease is just 18%. In the continued absence of an effective early detection test for
ovarian cancer, there is a considerable need to develop treatment strategies that can either circumvent (e.g. gene therapy) or prevent the development of
platinum resistance. A prerequisite for the development of such treatments is a detailed knowledge of factors that confer
tumor cell resistance to
platinum compounds. We have used surface-enhanced
laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS or SELDI) to identify low mass
proteins that are uniquely expressed in ovarian
tumor cells that are
platinum-resistant. Only two
polypeptide peaks (m/z 5041 and 7324) were consistently altered following the induction of
cisplatin resistance in the OAW42 and 2780 cell lines. These peaks appear to be specific to
cisplatin resistance as they are not altered in the same manner in a
melphalan-resistant variant of OAW42. The exact identity of the
polypeptide peaks is unknown, but appears to be unrelated to changes in several
proteins that have been historically associated with
cisplatin resistance. These data suggest that SELDI-based proteomic profiling may be useful in monitoring the emergence of
cisplatin-resistant
tumor cell clones.