The role of ABC transporters in anticancer drug transport

The main clinical problem in cancer treatment is the development of multidrug resistance. Tumors can be intrinsically drug-resistant or develop resistance to chemotherapy. Multidrug resistance can develop by diverse mechanisms including decreased rate of drug uptake, increased drug efflux, alterations in drug metabolism, mutation of drug targets, activation of DNA repair mechanisms, and evasion of apoptosis. The use of modern genomic, proteomic, bioinformatic, and systems biology approaches has resulted in a substantial increase in our ability to identify molecular mechanisms that are involved in multidrug resistance in cancer and to find drugs that may block or reverse the development of drug resistance.

Anahtar Kelimeler:

ABC transporters, cancer, neoplasm, P-glycoprotein, chemotherapy, multidrug resistance, tumor biology

The role of ABC transporters in anticancer drug transport

Keywords:

ABC transporters, cancer, neoplasm, P-glycoprotein, chemotherapy, multidrug resistance, tumor biology,

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Abolhoda A, Wilson AE, Ross H, Danenberg PV, Burt M, Scotto KW (1999). Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin Cancer Res 5: 3352–3356.
Advani R, Lum BL, Fisher GA, Halsey J, Chin DL, Jacobs CD, Sikic BI (2005). A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance. Ann Oncol 16: 1968–1973.
Albrecht C, Viturro E (2007). The ABCA subfamily - gene and protein structures, functions and associated hereditary diseases. Pflugers Arch 453: 581–589.
Ambudkar SV (1999). Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 39: 361–398.
Baekelandt M, Lehne G, Trope CG, Szanto I, Pfeiffer P, Gustavssson B, Kristensen GB (2001). Phase I/II trial of the multidrugresistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer. J Clin Oncol 19: 2983–2993.
Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM, Bumol TF, Starling JJ (1996). Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res 56: 4171–4179.
Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS, Binkley SN, Kuhfeld MT, Starling JJ, Wrighton SA (1999). Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther 290: 854–862.
Dean M (2005). The genetics of ATP-binding cassette transporters. Methods Enzymol 400: 409–429.
Dean M (2009). ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 14: 3–9.
Dean M, Rzhetsky A, Allikmets R (2001). The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11: 1156–1166.
Ferry DR, Traunecker H, Kerr DJ (1996). Clinical trials of P-glycoprotein reversal in solid tumours. Eur J Cancer 32: 1070–1081.
Fletcher JI, Haber M, Henderson MJ, Norris MD (2010). ABC transporters in cancer: more than just drug efflux pumps. Nat Rev Cancer 10: 147–156.
Fracasso PM, Brady MF, Moore DH, Walker JL, Rose PG, Letvak L, Grogan TM, McGuire WP (2001). Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol 19: 2975–2982.
Garraway LA, Chabner B (2002). MDR1 inhibition: less resistance or less relevance? Eur J Cancer 38: 2337–2340.
Gottesman MM, Fojo T, Bates SE (2002). Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Rev Cancer 2: 48–58.
Greenberg PL (2004). Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 22: 1078– 1086.
Haber M (2006). Association of high-level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma. J Clin Oncol 24: 1546–1553.
Hanada S (2008). Expression profile of early lung adenocarcinoma: identification of MRP3 as a molecular marker for early progression. J Pathol 216: 75–82.
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG (2013). Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13: 714–726.
Konig J (2005). Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. Int J Cancer 115: 359–367.
Krishna R, Mayer LD (2000). Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci 11: 265–283.
Lhomme C (2008). Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol 26: 2674–2682.
Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH (2001). Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7: 935–941.
Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007). Neuroblastoma. Lancet 369: 2106–2120.
Mistry P, Stewart AJ, Dangerfield W, Baker M, Liddle C, Bootle D, Kofler B, Laurie D, Denny WA, Baguley B et al. (2002). In vitro and in vivo characterization of XR11576, a novel, orally active, dual inhibitor of topoisomerase I and II. Anticancer Drugs 13: 15–28.
Mochida Y (2003). The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in ApcMin/+ mice. Carcinogenesis 24: 1219–1224.
Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S, Moran EJ, Uyeda RT, Dixon R, Guns ES et al. (2000). Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res 60: 2964–2972.
Oberthuer A (2006). Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification. J Clin Oncol 24: 5070–5078.
Oda Y (2005). ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas. Int J Cancer 114: 854–862.
Oevermann L (2009). Hematopoietic stem cell differentiation affects expression and function of MRP4 (ABCC4), a transport protein for signaling molecules and drugs. Int J Cancer 124: 2303–2311.
Ohtsuki S (2007). Correlation of induction of ATP binding cassette transporter A5 (ABCA5) and ABCB1 mRNAs with differentiation state of human colon tumor. Biol Pharm Bull 30: 1144–1146.
Relling MV (1996). Are the major effects of P-glycoprotein modulators due to altered pharmacokinetics of anticancer drugs? Ther Drug Monit 18: 350–356.
Roe M, Folkes A, Ashworth P, Brumwell J, Chima L, Hunjan S, Pretswell I, Dangerfield W, Ryder H, Charlton P (1999).
Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett 9: 595–600.
Schinkel AH (1994). Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77: 491–502.
Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O et al. (1997). Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. P Natl Acad Sci USA 94: 4028–4033.
Shepard RL, Cao J, Starling JJ, Dantzig AH (2003). Modulation of P-glycoprotein but not MRP1- or BCRP-mediated drug resistance by LY335979. Int J Cancer 103: 121–125.
Starling JJ, Shepard RL, Cao J, Law KL, Norman BH, Kroin JS, Ehlhardt WJ, Baughman TM, Winter MA, Bell MG et al. (1997). Pharmacological characterization of LY335979: a potent cyclopropyldibenzosuberane modulator of P-glycoprotein. Adv Enzyme Regul 37: 335–347.
Steinbach D (2006). ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. Clin Cancer Res 12: 4357–4363.
Szakacs G (2004). Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 6: 129–137.
te Boekhorst PA, van Kapel J, Schoester M, Sonneveld P (1992). Reversal of typical multidrug resistance by cyclosporin and its non-immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing the mdr1 phenotype. Cancer Chemother Pharmacol 30: 238–242.
Thomas H, Coley HM (2003). Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting P-glycoprotein. Cancer Control 10: 159–165.
Twentyman PR, Bleehen NM (1991). Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin [corrected]. Eur J Cancer 27: 1639–1642.
Vander Borght S (2008). Expression of multidrug resistanceassociated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin. Liver Int 28: 1370–1380.
van Zuylen L, Nooter K, Sparreboom A, Verweij J (2000). Development of multidrug-resistance convertors: sense or nonsense? Invest New Drugs 18: 205–220.
Weinstein RS (1991). Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymph node metastasis. Cancer Res 51: 2720–2726.
Yamada T (2003). Suppression of intestinal polyposis in Mdr1- deficient ApcMin/+ mice. Cancer Res 63: 895–901.
Yoh K (2004). Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced nonsmall cell lung cancer. Clin Cancer Res 10: 1691–1697.
Zochbauer-Muller S (2001). P-glycoprotein and MRP1 expression in axillary lymph node metastases of breast cancer patients. Anticancer Res 21: 119–124.