Targeting the PI3K-Akt pathway in kidney cancer

Expert Review of Anticancer Therapy

Volumn 7, Issue 6, 2007, Pages 863-870

  Park, Jin Young ^a   Lin, Pei Yin ^a,b   Weiss, Robert H ^a,c  

^a Division of Nephrology   (United States)

^b Center for Hematology Oncology   (United States)

^c Northern California Health Care System   (United States)

Author keywords

Akt; Inhibitors; PI3K; Receptor tyrosine kinase; Renal cell carcinoma

Indexed keywords

17 HYDROXYWORTMANNIN; 2 MORPHOLINO 8 PHENYLCHROMONE; 6 HYDROXYMETHYL CHIRO INOSITOL 2 O METHYL 3 O OCTADECYLCARBONATE; ALPHA INTERFERON; ANTINEOPLASTIC AGENT; BALANOL; BEVACIZUMAB; EVEROLIMUS; FLUOROURACIL; FOLINIC ACID; INOSITOL DERIVATIVE; INOSITOL PENTAKISPHOSPHATE; INTERFERON; INTERLEUKIN 2; IRINOTECAN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; N [2 (4 BROMOCINNAMYLAMINO)ETHYL] 5 ISOQUINOLINESULFONAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PLACEBO; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; PWT 458; RAPAMYCIN; SORAFENIB; SUNITINIB; TEMSIROLIMUS; THALIDOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; WORTMANNIN;

ASTHENIA; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CLINICAL TRIAL; CYTOTOXICITY; DIARRHEA; DOWN REGULATION; DRUG ERUPTION; DRUG MEGADOSE; DRUG TARGETING; ENZYME INHIBITION; FATIGUE; GENE MUTATION; GENE TARGETING; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; IMMUNOHISTOCHEMISTRY; KIDNEY CANCER; KIDNEY CARCINOMA; MITOGENESIS; MUCOSA INFLAMMATION; NAUSEA; NONHUMAN; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN STRUCTURE; PROTEINURIA; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; STOMATITIS; STRUCTURE ANALYSIS; UNSPECIFIED SIDE EFFECT; UPREGULATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; ANTINEOPLASTIC AGENTS; ENZYME INHIBITORS; HUMANS; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 34347244544     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/14737140.7.6.863     Document Type: Review

References (51)

1. Weiss RH, Lin P-Y. Kidney cancer: identification of novel targets for therapy. Kidney Int. 69, 224-232 (2006).
2. Tuma RS. Three molecularly targeted drugs tested in kidney cancer clinical trials. J. Natl Cancer Inst. 96, 1270-1271 (2004).
3. Nanus DM, Garino A, Milowsky MI, Larkin M, Dutcher JP. Active chemotherapy for sarcomatoid and rapidly progressing renal call carcinoma. Cancer 101, 1545-1551 (2004).
4. Vuky J, Motzer RJ. Cytokine therapy in renal cell cancer. Urol. Oncol. 5, 249-257 (2000).
5. Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Fyfe G. High-dose aldesleukin in renal cell carcinoma: long-term survival update. Cancer J. Sci. Am. 3(Suppl. 1), S70-S72 (1997).
6. Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356, 125-134 (2007).
7. Chabner BA, Roberts TG Jr. Timeline: chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65-72 (2005).
8. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 14, 381-395 (2002).
9. Hanada M, Feng J, Hemmings BA. Structure, regulation and function of PKB/ AKT - a major therapeutic target. Biochim. Biophys. Acta 1697, 3-16 (2004).
10. Horiguchi A, Oya M, Uchida A, Marumo K, Murai M. Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma. J. Urol. 169, 710-713 (2003).
11. Sourbier C, Lindner V, Lang H et al. The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Cancer Res. 66, 5130-5142 (2006).
12. Lee JS, Kim HS, Kim YB, Lee MC, Park CS. Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth. J. Surg. Oncol. 84, 166-172 (2003).
13. Hara S, Oya M, Mizuno R, Horiguchi A, Marumo K, Murai M. Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor. Ann. Oncol. 16, 928-933 (2005).
14. Brenner W, Farber G, Herget T, Lehr HA, Hengstler JG, Thuroff JW. Loss of tumor suppressor protein PTEN during renal carcinogenesis. Int. J. Cancer 99, 53-57 (2002).
15. Alimov A, Li C, Gizatullin R et al. Somatic mutation and homozygous deletion of PTEN/MMAC1 gene of 10q23 in renal cell carcinoma. Anticancer Res. 19, 3841-3846 (1999).
16. Sukosd F, Digon B, Fischer J, Pietsch T, Kovacs G. Allelic loss at 10q23.3 but lack of mutation of PTEN/MMAC1 in chromophobe renal cell carcinoma. Cancer Genet. Cytogenet. 128, 161-163 (2001).
17. Figlin RA, Seligson D, Wu H et al. Characterization of the tutor pathway in renal cell carcinoma and its use in predicting patient selection for agents targeting this pathway, J. Clin. Oncol. 23(16 Suppl.) (2005) (Abstract 4539).
18. Eng C. PTEN: one gene, many syndromes. Hum. Mutat. 22, 183-198 (2003).
19. Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9, 667-676 (2004).
20. Wymann MP, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim. Biophys. Acta 1436, 127-150 (1998).
21. Yang JC, Haworth L, Sherry RM et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med. 349, 427-434 (2003).
22. Elaraj DM, White DE, Steinberg SM, Haworth L, Rosenberg SA, Yang JC. A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma. J. Immunother. 27, 259-264 (2004).
23. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335-2342 (2004).
24. Rini BI, Halabi S, Taylor J, Small EJ, Schilsky RL. Cancer and Leukemia Group B 90206: a randomized Phase III trial of interferon-α or interferon-α plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin. Cancer Res. 10, 2584-2586 (2004).
25. Motzar RJ, Rini BI, Bukowski RM et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295, 2516-2524 (2006).
26. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon-α in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115-124 (2007).
27. Flaherty KT. Sorafenib in renal cell carcinoma. Clin. Cancer Res. 13, S747-S752 (2007).
28. Wiesinger D, Gubler HU, Haefliger W, Hauser D. Antiinflammatory activity of the new mould metabolite 11-desacetoxy-wortmannin and of some of its derivatives. Experientia 30, 135-136 (1974).
29. Wymann MP. Bulgarelli-Leva G, Zvelebil MJ et al. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol. Cell Biol. 16, 1722-1733 (1996).
30. Wetzker R, Rommel C. Phosphoinositide 3-kinases as targets for therapeutic intervention. Curr. Pharm. Des. 10, 1915-1922 (2004).
31. Davies SP, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105 (2000).
32. Ng SSW, Tsao MS, Chow S, Hedley DW. Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res. 60, 5451-5455 (2000).
33. Ng SS, Tsao MS, Nicklee T, Hedley DW. Wortmannin inhibits PKB/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin. Cancer Res. 7, 3269-3275 (2001).
34. Gupta AK, Cerniglia GJ, Mick R et al. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int. J Radiat. Oncol. Biol. Phys. 56, 846-853 (2003).
35. Yu K, Lucas J, Zhu T et al. PWT-458, a novel pegylated-17-hydroxywortmannin, inhibits phosphatidylinositol 3-kinase signaling and suppresses growth of solid tumors. Cancer Biol. Ther. 4, 538-545 (2005).
36. Breitenlechner CB, Wegge T, Berillon L et al. Structure-based optimization of novel azepane derivatives as PKB inhibitors. J. Med. Chem. 47, 1375-1390 (2004).
37. Chijiwa T, Mishima A, Hagiwara M et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N- [2- (p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J. Biol. Chem. 265, 5267-5272 (1990).
38. Redaelli C, Granucci F, De Gioia L, Cipolla L. Synthesis and biological activity of Akt/PI3K inhibitors. Mini Rev. Med. Chem. 6, 1127-1136 (2006).
39. Gills JJ, Holbeck S, Hollingshead M, Hewitt SM, Kozikowski AR, Dennis PA. Spectrum of activity and molecular correlates of response to phosphatidylinositol ether lipid analogues, novel lipid-based inhibitors of Akt. Mol. Cancer Ther. 5, 713-722 (2006).
40. Maffucci T, Piccolo E, Cumashi A et al. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects. Cancer Res. 65, 8339-8349 (2005).
41. Piccolo E, Vignati S, Maffucci T et al. Inositol pentakisphosphate promotes apoptosis through the PI3-K/Akt pathway. Oncogene 23, 1754-1765 (2004).
42. Claerhout S, Decraene D, Van Laethem A, Van Kelst S, Agostinis P, Garmyn M. AKT delays the early-activated apoptotic pathway in UVB-irradiated keratinocytes via BAD translocation. J. Invest Dermatol. 127, 429-438 (2007).
43. Liou JY, Ghelani D, Yeh S, Wu KK. Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3ε. Cancer Res. 67, 3185-3191 (2007).
44. Kubo S, Doe I, Kurokawa Y, Nishikawa H, Kawabata A. Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension. Toxicology 232, 138-146 (2007).
45. Wiederrecht GJ, Sabers CJ, Brunn GJ, Martin MM, Dumont FJ, Abraham RT. Mechanism of action of rapamycin: new insights into the regulation of G1-phase progression in eukaryotic cells. Prog. Cell Cycle Res. 1, 53-71 (1995).
46. 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).
47. Luan FL, Ding R, Sharma VK, Chon WJ, Lagman M, Suthanthiran M. Rapamycin is an effective inhibitor of human renal cancer metastasis. Kidney Int. 63, 917-926 (2003).
48. Atkins MB, Hidalgo M, Stadler WM et al. Randomized Phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma, J. Clin. Oncol. 22, 909-918 (2004).
49. Hudes G, Carducci M, Tomczak P et al. A Phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-α (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cell carcinoma. Proc. Ann. Meet. Am. Soc. Clin. Oncol. 24(Suppl.) S18 (2006).
50. Beuvink I, Boulay A, Fumagalli S et al. The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damage-induced apoptosis through inhibition of p21 translation. Cell 120, 747-759 (2005).
51. Weiss RH. p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4, 425-429 (2003).