Small-molecule inhibitors of p21 as novel therapeutics for chemotherapy-resistant kidney cancer

Future Medicinal Chemistry

Volumn 5, Issue 9, 2013, Pages 991-994

  Liu, Ruiwu ^a   Wettersten, Hiromi I ^a   Park, See Hyoung ^b   Weiss, Robert H ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

apoptosis; chemoresistance; kidney cancer; p21; small molecule inhibitor

Indexed keywords

BUTYROLACTONE; DOXORUBICIN; LLW 10; PROTEIN INHIBITOR; PROTEIN P21; SORAFENIB; UC 2288; UNCLASSIFIED DRUG;

APOPTOSIS; CANCER INHIBITION; DNA DAMAGE; G1 PHASE CELL CYCLE CHECKPOINT; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; KIDNEY CANCER; M PHASE CELL CYCLE CHECKPOINT; NOTE; PRIORITY JOURNAL; THERAPY RESISTANCE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE CHECKPOINTS; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DRUG RESISTANCE, NEOPLASM; HUMANS; KIDNEY NEOPLASMS; RNA INTERFERENCE; RNA, SMALL INTERFERING; SMALL MOLECULE LIBRARIES;

EID: 84878726714     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.13.56     Document Type: Note

References (19)

1. Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat. Rev. Cancer 5(3), 231-237 (2005).
2. Gartel AL, Tyner AL. The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol. Cancer Ther. 1(8), 639-649 (2002).
3. Weiss RH. p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4(6), 425-429 (2003).
4. Cmielova J, Rezacova M. p21Cip1/Waf1 protein and its function based on a subcellular localization [corrected]. J. Cell. Biochem. 112(12), 3502-3506 (2011).
5. Asada M, Yamada T, Ichijo H, et al. Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. EMBO J. 18(5), 1223-1234 (1999).
6. Klopfleisch R, Gruber AD. Differential expression of cell cycle regulators p21, p27 and p53 in metastasizing canine mammary adenocarcinomas versus normal mammary glands. Res. Vet. Sci. 87(1), 91-96 (2009).
7. Weiss RH, Borowsky AD, Seligson D, et al. p21 is a prognostic marker for renal cell carcinoma: implications for novel therapeutic approaches. J. Urol. 177(1), 63-69 (2007).
8. Park SH, Park JY, Weiss RH. Antisense attenuation of p21 sensitizes kidney cancer to apoptosis in response to conventional DNA damaging chemotherapy associated with enhancement of phospho-p53. J. Urol. 180(1), 352-360 (2008).
9. Biankin AV, Kench JG, Morey AL, et al. Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res. 61(24), 8830-8837 (2001).
10. Lin PY, Fosmire SP, Park SH, et al. Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance. Mol. Cancer 6, 16 (2007).
11. Sax JK, Dash BC, Hong R, Dicker DT, El-Deiry WS. The cyclin-dependent kinase inhibitor butyrolactone is a potent inhibitor of p21 (WAF1/CIP1 expression). Cell Cycle 1(1), 90-96 (2002).
12. Park SH, Wang X, Liu R, Lam KS, Weiss RH. High throughput screening of a small molecule one-bead-one-compound combinatorial library to identify attenuators of p21 as chemotherapy sensitizers. Cancer Biol. Ther. 7(12), 2015-2022 (2008).
13. Inoue H, Hwang SH, Wecksler AT, Hammock BD, Weiss RH. Sorafenib attenuates p21 in kidney cancer cells and augments cell death in combination with DNA-damaging chemotherapy. Cancer Biol. Ther. 12(9), 827-836 (2011).
14. Wettersten HI, Hee Hwang S, Li C, et al. A novel p21 attenuator which is structurally related to sorafenib. Cancer Biol. Ther. 14(3), 278-285 (2013).
15. Inoue H, Kauffman M, Shacham S, et al. CRM1 blockade by selective inhibitors of nuclear export (SINE) attenuates kidney cancer growth. J. Urol. 189(6), 2317-2326 (2013).
16. Jung YS, Qian Y, Chen X. Examination of the expanding pathways for the regulation of p21 expression and activity. Cell. Signal. 22(7), 1003-1012 (2010).
17. Sugahara KN, Teesalu T, Karmali PP, et al. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science 328(5981), 1031-1035 (2010).
18. Burnett JC, Rossi JJ, Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol. J. 6(9), 1130-1146 (2011).
19. Pirollo KF, Xu L, Chang EH. Non-viral gene delivery for p53. Curr. Opin. Mol. Ther. 2(2), 168-175 (2000).