Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?
- PMID: 22724067
- PMCID: PMC3376736
- DOI: 10.1098/rsob.120066
Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?
Abstract
Although chemotherapy of tumours has scored successes, drug resistance remains the major cause of death of cancer patients. Initial treatment often leaves residual disease, from which the tumour regrows. Eventually, most tumours become resistant to all available chemotherapy. I call this pan-resistance to distinguish it from multi-drug resistance, usually describing resistance caused by upregulation of drug transporters, such as P-glycoprotein. In this review, I discuss mechanisms proposed to explain both residual disease and pan-resistance. Although plausible explanations are at hand for residual disease, pan-resistance is still a mystery. My conclusion is that it is time for a major effort to solve this mystery using the new genetically modified mouse tumour models that produce real tumours resembling cancer in human patients.
Keywords: drug resistance; epithelial to mesenchymal transition; multi-drug resistance; pan-resistance; persisters; residual disease.
References
-
- Swanton C, Nicke B, Marani M, Kelly G, Downward J. 2007. Initiation of high frequency multi-drug resistance following kinase targeting by siRNAs. Cell Cycle 6, 2001–200410.4161/cc.6.16.4538 (doi:10.4161/cc.6.16.4538) - DOI - DOI - PubMed
-
- Falagas ME, Karageorgopoulos DE. 2008. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli: need for international harmonization in terminology. Clin. Infect Dis. 46, 1121–112210.1086/528867 (doi:10.1086/528867) - DOI - DOI - PubMed
-
- Harris AL. 1985. DNA repair and resistance to chemotherapy. Cancer Surv. 4, 601–624 - PubMed
-
- Kaelin WG., Jr 2005. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5, 689–69810.1038/nrc1691 (doi:10.1038/nrc1691) - DOI - DOI - PubMed
-
- Chan DA, Giaccia AJ. 2011. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat. Rev. Drug Discov. 10, 351–36410.1038/nrd3374 (doi:10.1038/nrd3374) - DOI - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous