Mechanisms of Chemoresistance in Cancer Stem Cells

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2013 Feb 2

PMID 23369605

Citations 373

Authors

Lissa Nurrul Abdullah

Edward Kai-Hua Chow

Affiliations

Soon will be listed here.

Abstract

Chemotherapy is one of the standard methods of treatment in many cancers. While chemotherapy is often capable of inducing cell death in tumors and reducing the tumor bulk, many cancer patients experience recurrence and ultimately death because of treatment failure. In recent years, cancer stem cells (CSCs) have gained intense interest as key tumor-initiating cells that may also play an integral role in recurrence following chemotherapy. As such, a number of mechanisms of chemoresistance have been identified in CSCs. In this review, we describe a number of these mechanisms of chemoresistance including ABC transporter expression, aldehyde dehydrogenase (ALDH) activity, B-cell lymphoma-2 (BCL2) related chemoresistance, enhanced DNA damage response and activation of key signaling pathways. Furthermore, we evaluate studies that demonstrate potential methods for overcoming chemoresistance and treating chemoresistant cancers that are driven by CSCs. By understanding how tumor-initiating cells such as CSCs escape chemotherapy, more informed approaches to treating cancer will develop and may improve clinical outcomes for cancer patients.

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References

Chow E, Zhang X, Chen M, Lam R, Robinson E, Huang H . Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci Transl Med. 2011; 3(73):73ra21. DOI: 10.1126/scitranslmed.3001713. View

Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

Singh S, Clarke I, Terasaki M, Bonn V, Hawkins C, Squire J . Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63(18):5821-8. View

Kelly P, Strasser A . The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 2011; 18(9):1414-24. PMC: 3149740. DOI: 10.1038/cdd.2011.17. View

Ulasov I, Nandi S, Dey M, Sonabend A, Lesniak M . Inhibition of Sonic hedgehog and Notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol Med. 2010; 17(1-2):103-12. PMC: 3022974. DOI: 10.2119/molmed.2010.00062. View

Hilton J . Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res. 1984; 44(11):5156-60. View

Haraguchi N, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Sasaki A . Cancer stem cells in human gastrointestinal cancers. Hum Cell. 2006; 19(1):24-9. DOI: 10.1111/j.1749-0774.2005.00004.x. View

Ranganathan P, Weaver K, Capobianco A . Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011; 11(5):338-51. DOI: 10.1038/nrc3035. View

Lin T, Matsui W . Hedgehog pathway as a drug target: Smoothened inhibitors in development. Onco Targets Ther. 2012; 5:47-58. PMC: 3325001. DOI: 10.2147/OTT.S21957. View

10.

Szotek P, Pieretti-Vanmarcke R, Masiakos P, Dinulescu D, Connolly D, Foster R . Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A. 2006; 103(30):11154-9. PMC: 1544057. DOI: 10.1073/pnas.0603672103. View

11.

Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

12.

Dalton W, Crowley J, Salmon S, Grogan T, Laufman L, Weiss G . A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A Southwest Oncology Group study. Cancer. 1995; 75(3):815-20. DOI: 10.1002/1097-0142(19950201)75:3<815::aid-cncr2820750311>3.0.co;2-r. View

13.

Friedman H, COLVIN O, Kaufmann S, Ludeman S, Bullock N, Bigner D . Cyclophosphamide resistance in medulloblastoma. Cancer Res. 1992; 52(19):5373-8. View

14.

Hellsten R, Johansson M, Dahlman A, Sterner O, Bjartell A . Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells. PLoS One. 2011; 6(7):e22118. PMC: 3133629. DOI: 10.1371/journal.pone.0022118. View

15.

Sladek N . Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol. 2003; 17(1):7-23. DOI: 10.1002/jbt.10057. View

16.

Ikawa M, Impraim C, Wang G, Yoshida A . Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983; 258(10):6282-7. View

17.

Duong H, Hwang J, Kim H, Kang H, Seong Y, Bae I . Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. Int J Oncol. 2012; 41(3):855-61. PMC: 3508685. DOI: 10.3892/ijo.2012.1516. View

18.

Noda T, Nagano H, Takemasa I, Yoshioka S, Murakami M, Wada H . Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer. 2009; 100(10):1647-58. PMC: 2696759. DOI: 10.1038/sj.bjc.6605064. View

19.

Macconaill L, Garraway L . Clinical implications of the cancer genome. J Clin Oncol. 2010; 28(35):5219-28. PMC: 3020694. DOI: 10.1200/JCO.2009.27.4944. View

20.

Longley D, Johnston P . Molecular mechanisms of drug resistance. J Pathol. 2005; 205(2):275-92. DOI: 10.1002/path.1706. View