Drug resistance reversal--are we getting closer?
Clinical drug resistance is a major barrier to overcome before chemotherapy can become curative for most patients presenting with metastatic cancer. Rational attempts to tackle clinical drug resistance need to be based on an understanding of the mechanisms involved; these are likely to be complex and multifactorial, and may be due to inadequate drug exposure or alterations in the cancer cell itself. This article reviews a number of strategies used to tackle drug resistance, focussing on work in our institution related to the treatment of ovarian cancer and resistance to platinum and taxane-based chemotherapy. Further progress towards drug resistance reversal will require a three-pronged approach, namely: the development of novel cytotoxics which exploit selectively expressed targets; modulation of resistance to conventional agents and, most importantly, a serious attempt to understand resistance mechanisms in tumour samples taken both pre- and post-chemotherapy.
Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
R D
RD
Baird
S B
SB
Kaye
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020137:Base Pair Mismatch; D016190:Carboplatin / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000737:chemistry / Q000627:therapeutic use; D017671:Platinum Compounds / Q000737:chemistry / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D014404:Tubulin / Q000235:genetics
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D014404:Tubulin; D016190:Carboplatin; D017239:Paclitaxel