Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2012, Article ID 382159, 7 pages
http://dx.doi.org/10.1155/2012/382159
Review Article

Special Agents Hunting Down Women Silent Killer: The Emerging Role of the p38α Kinase

Laboratory of Signal-dependent Transcription, Department of Translational Pharmacology (DTP), Consorzio Mario NegriSud 66030, Santa Maria Imbaro, Italy

Received 20 September 2011; Revised 21 December 2011; Accepted 29 December 2011

Academic Editor: Ritu Salani

Copyright © 2012 Valentina Grossi and Cristiano Simone. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. A. Yap, C. P. Carden, and S. B. Kaye, “Beyond chemotherapy: targeted therapies in ovarian cancer,” Nature Reviews Cancer, vol. 9, no. 3, pp. 167–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. J. S. Berek, “Epithelial ovarian cancer,” in Practical Gynecologic Oncology 4th edn Ch. 11 Ovarian Cancer, J. S. Berek and N. F. Hacker, Eds., pp. 443–511, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 2005. View at Google Scholar
  3. P. Watson and H. T. Lynch, “Extracolonic cancer in hereditary nonpolyposis colorectal cancer,” Cancer, vol. 71, no. 3, pp. 677–685, 1993. View at Google Scholar · View at Scopus
  4. S. C. Rubin, M. A. Blackwood, C. Bandera et al., “BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing,” American Journal of Obstetrics and Gynecology, vol. 178, no. 4, pp. 670–677, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. G. Singer, R. Oldt III, Y. Cohen et al., “Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma,” Journal of the National Cancer Institute, vol. 95, no. 6, pp. 484–486, 2003. View at Google Scholar · View at Scopus
  6. K. Nakayama, N. Nakayama, R. J. Kurman et al., “Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms,” Cancer Biology and Therapy, vol. 5, no. 7, pp. 779–785, 2006. View at Google Scholar · View at Scopus
  7. D. M. Dinulescu, T. A. Ince, B. J. Quade, S. A. Shafer, D. Crowley, and T. Jacks, “Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer,” Nature Medicine, vol. 11, no. 1, pp. 63–70, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Oliva, E. F. Sarrió, E. F. Brachtel et al., “High frequency of β-catenin mutations in borderline endometrioid tumours of the ovary,” Journal of Pathology, vol. 208, no. 5, pp. 708–713, 2006. View at Publisher · View at Google Scholar
  9. R. Wu, N. Hendrix-Lucas, R. Kuick et al., “Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways,” Cancer Cell, vol. 11, no. 4, pp. 321–333, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. K. W. Cheng, J. P. Lahad, J. W. Gray, and G. B. Mills, “Emerging role of RAB GTPases in cancer and human disease,” Cancer Research, vol. 65, no. 7, pp. 2516–2519, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. I. Chefetz, J. C. Holmberg, A. B. Alvero, I. Visintin, and G. Mor, “Inhibition of Aurora-A kinase induces cell cycle arrest in epithelial ovarian cancer stem cells by affecting NFκB pathway,” Cell Cycle, vol. 10, no. 13, pp. 2206–2214, 2011. View at Publisher · View at Google Scholar
  12. S. Jones, T. L. Wang, I. M. Shih et al., “Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma,” Science, vol. 330, no. 6001, pp. 228–231, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. K. C. Wiegand, S. P. Shah, O. M. Al-Agha et al., “ARID1A mutations in endometriosis-associated ovarian carcinomas,” New England Journal of Medicine, vol. 363, no. 16, pp. 1532–1543, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. B. Guan, T.-L. Mao, P. K. Panuganti et al., “Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma,” American Journal of Surgical Pathology, vol. 35, no. 5, pp. 625–632, 2011. View at Publisher · View at Google Scholar
  15. B. Guan, T.-L. Wang, and I.-M. Shih, “ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers,” Cancer Research, vol. 71, no. 21, pp. 6718–6727, 2011. View at Publisher · View at Google Scholar
  16. Z. Lu, R. Z. Luo, Y. Lu et al., “The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells,” Journal of Clinical Investigation, vol. 118, no. 12, pp. 3917–3929, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Yu, F. Xu, H. Peng et al., “NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 1, pp. 214–219, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Z. Luo, H. Peng, F. Xu et al., “Genomic structure and promoter characterization of an imprinted tumor suppressor gene ARHI,” Biochimica et Biophysica Acta, vol. 1519, no. 3, pp. 216–222, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. D. G. Rosen, L. Wang, A. N. Jain et al., “Expression of the tumor suppressor gene ARHI in epithelial ovarian cancer is associated with increased expression of p21WAF1/CIP1 and prolonged progression-free survival,” Clinical Cancer Research, vol. 10, no. 19, pp. 6559–6566, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Kondo, T. Kanzawa, R. Sawaya, and S. Kondo, “The role of autophagy in cancer development and response to therapy,” Nature Reviews Cancer, vol. 5, no. 9, pp. 726–734, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Marx, “Autophagy: is it cancer's friend or foe?” Science, vol. 312, no. 5777, pp. 1160–1161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Degenhardt, R. Mathew, B. Beaudoin et al., “Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis,” Cancer Cell, vol. 10, no. 1, pp. 51–64, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. J. S. Carew, S. T. Nawrocki, C. N. Kahue et al., “Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHAto overcome Bcr-Abl-mediated drug resistance,” Blood, vol. 110, no. 1, pp. 313–322, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. Z. Lu, R. Z. Luo, Y. Lu et al., “A novel tumor suppressor gene ARHI induces autophagy and tumor dormancy in ovarian cancer xenografts,” Journal of Clinical Investigation, vol. 118, pp. 3917–3929, 2008. View at Google Scholar
  25. W. Feng, R. T. Marquez, Z. Lu et al., “Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation,” Cancer, vol. 112, no. 7, pp. 1489–1502, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. B. Rosenberg, L. VanCamp, J. E. Trosko, and V. H. Mansour, “Platinum compounds: a new class of potent antitumour agents,” Nature, vol. 222, no. 5191, pp. 385–386, 1969. View at Publisher · View at Google Scholar · View at Scopus
  27. C. W. Helm and J. C. States, “Enhancing the efficacy of cisplatin in ovarian cancer treatment—could arsenic have a role,” Journal of Ovarian Research, vol. 2, no. 1, article 2, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. R. E. Bristow, R. S. Tomacruz, D. K. Armstrong, E. L. Trimble, and F. J. Montz, “Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis,” Journal of Clinical Oncology, vol. 20, no. 5, pp. 1248–1259, 2002. View at Publisher · View at Google Scholar · View at Scopus
  29. R. F. Ozols, B. N. Bundy, B. E. Greer et al., “Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study,” Journal of Clinical Oncology, vol. 21, no. 17, pp. 3194–3200, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. W. P. McGuire, M. F. Brady, and R. F. Ozols, “The Gynecologic Oncology Group experience in ovarian cancer,” Annals of Oncology, vol. 10, supplement 1, pp. S29–S34, 1999. View at Google Scholar · View at Scopus
  31. J. Yoneda, H. Kuniyasu, M. A. Crispens, J. E. Price, C. D. Bucana, and I. J. Fidler, “Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice,” Journal of the National Cancer Institute, vol. 90, no. 6, pp. 447–454, 1998. View at Google Scholar · View at Scopus
  32. M. J. Birrer, M. E. Johnson, K. Hao et al., “Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas,” Journal of Clinical Oncology, vol. 25, no. 16, pp. 2281–2287, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. B. J. Monk, E. Han, C. A. Josephs-Cowan, G. Pugmire, and R. A. Burger, “Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytoxic regimens in advanced refractory epithelial ovarian cancer,” Gynecologic Oncology, vol. 102, pp. 140–144, 2006. View at Google Scholar
  34. A. A. Kamat, T. J. Kim, C. N. Landen et al., “Metronomic chemotherapy enhances the efficacy of antivascular therapy in ovarian cancer,” Cancer Research, vol. 67, no. 1, pp. 281–288, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Lu, P. H. Thaker, Y. G. Lin et al., “Impact of vessel maturation on antiangiogenic therapy in ovarian cancer,” American Journal of Obstetrics and Gynecology, vol. 198, no. 4, pp. 477–479, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. J. J. Biagi, A. M. Oza, H. I. ChalChal et al., “A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC clinical trials group study,” Annals of Oncology, vol. 22, no. 2, pp. 335–340, 2011. View at Publisher · View at Google Scholar
  37. H. W. Hirte, L. Vidal, and G. F. Fleming, “Aphase II study of cediranib (AZD2171) in recurrent or persistent ovarian, peritonealor fallopian tube cancer: final results of aPMH, Chicago and California consortiatrial,” in Proceedings of the 44th American Society of Clinical OncologyAnnual Meeting of the Program and Abstracts, Chicago, Ill, USA, May-June 2008.
  38. R. J. Schilder, M. W. Sill, X. Chen et al., “Phase II study of gefitinib inpatients with relapsed or persistent ovarian or primaryperitoneal carcinoma and evaluation of epidermalgrowth factor receptor mutations andimmunohistochemical expression: a Gynecologic Oncology Group Study,” Clinical Cancer Research, vol. 11, pp. 5539–5548, 2005. View at Google Scholar
  39. A. N. Gordon, N. Finkler, R. P. Edwards et al., “Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study,” International Journal of Gynecological Cancer, vol. 15, no. 5, pp. 785–792, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. V. Heinemann, S. Stintzing, T. Kirchner, S. Boeck, and A. Jung, “Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR,” Cancer Treatment Reviews, vol. 35, no. 3, pp. 262–271, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. H. S. Cho, K. Mason, K. X. Ramyar et al., “Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab,” Nature, vol. 421, no. 6924, pp. 756–760, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. M. C. Franklin, K. D. Carey, F. F. Vajdos, D. J. Leahy, A. M. De Vos, and M. X. Sliwkowski, “Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex,” Cancer Cell, vol. 5, no. 4, pp. 317–328, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Makhija, L. C. Amler, D. Glenn et al., “Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer,” Journal of Clinical Oncology, vol. 28, no. 7, pp. 1215–1223, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. S. B. Kaye, C. J. Poole, and M. Bidzinksi, “A randomised phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin based therapy alone in patients with relapsed, platinum sensitive ovarian cancer,” Journal of Clinical Oncology, vol. 26, abstract 5520, 2008. View at Google Scholar
  45. D. Faratian, A. J.M. Zweemer, Y. Nagumo et al., “Trastuzumab and pertuzumab produce changes in morphology and estrogen receptor signaling in ovarian cancer xenografts revealing new treatment strategies,” Clinical Cancer Research, vol. 17, no. 13, pp. 4451–4461, 2011. View at Publisher · View at Google Scholar
  46. L. Hu, J. Hofmann, Y. Lu, G. B. Mills, and R. B. Jaffe, “Inhibition of phosphatidylinositol 3′-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models,” Cancer Research, vol. 62, no. 4, pp. 1087–1092, 2002. View at Google Scholar · View at Scopus
  47. F. I. Raynaud, S. Eccles, P. A. Clarke et al., “Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases,” Cancer Research, vol. 67, no. 12, pp. 5840–5850, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. J. S. McMurray, “A new small-molecule Stat3 inhibitor,” Chemistry and Biology, vol. 13, no. 11, pp. 1123–1124, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. H. P. Beck, T. Kohn, S. Rubenstein et al., “Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 3, pp. 1037–1041, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. G. Lin, A. B. Kunnumakkara, A. Nair et al., “Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway,” Clinical Cancer Research, vol. 13, no. 11, pp. 3423–3430, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. A. K. Samanta, H. J. Huang, R. C. Bast, and W. S. L. Liao, “Overexpression of MEKK3 confers resistance to apoptosis through activation of NFκB,” Journal of Biological Chemistry, vol. 279, no. 9, pp. 7576–7583, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Karin, “Nuclear factor-κB in cancer development and progression,” Nature, vol. 441, no. 7092, pp. 431–436, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Ashworth, “A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair,” Journal of Clinical Oncology, vol. 26, no. 22, pp. 3785–3790, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. P. C. Fong, D. S. Boss, and C. P. Carden, “AZD2281 (KU-0059436), a PARP (poly ADP-ribose polymerase) inhibitor with single agent anticancer activity in patients with BRCA deficient ovarian cancer: results from a phase I study,” Journal of Clinical Oncology, vol. 26, abstract 5510, 2008. View at Google Scholar
  55. A. Mangerich and A. Bürkle, “How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation,” International Journal of Cancer, vol. 128, no. 2, pp. 251–265, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. N. C. Denko, “Hypoxia, HIF1 and glucose metabolism in the solid tumour,” Nature Reviews Cancer, vol. 8, no. 9, pp. 705–713, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. S. S. Gambhir, “Molecular imaging of cancer with positron emission tomography,” Nature Reviews Cancer, vol. 2, no. 9, pp. 683–693, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. D. A. Mankoff, J. F. Eary, J. M. Link et al., “Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond,” Clinical Cancer Research, vol. 13, no. 12, pp. 3460–3469, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. G. Kroemer and J. Pouyssegur, “Tumor cell metabolism: cancer's achilles' heel,” Cancer Cell, vol. 13, no. 6, pp. 472–482, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. P. P. Hsu and D. M. Sabatini, “Cancer cell metabolism: warburg and beyond,” Cell, vol. 134, no. 5, pp. 703–707, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. E. Favaro, G. Nardo, L. Persano et al., “Hypoxia inducible factor-1α inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death,” American Journal of Pathology, vol. 173, no. 4, pp. 1186–1201, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. R. Shimogai, J. Kigawa, H. Itamochi et al., “Expression of hypoxia-inducible factor 1α gene affects the outcome in patients with ovarian cancer,” International Journal of Gynecological Cancer, vol. 18, no. 3, pp. 499–505, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. B. M. Emerling, L. C. Platanias, E. Black, A. R. Nebreda, R. J. Davis, and N. S. Chandel, “Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling,” Molecular and Cellular Biology, vol. 25, no. 12, pp. 4853–4862, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. S. J. Kwon, J. J. Song, and Y. J. Lee, “Signal pathway of hypoxia-inducible factor-1α phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells,” Clinical Cancer Research, vol. 11, no. 21, pp. 7607–7613, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. F. Chiacchiera and C. Simone, “Signal-dependent regulation of gene expression as a target for cancer treatment: inhibiting p38α in colorectal tumors,” Cancer Letters, vol. 265, no. 1, pp. 16–26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. F. Comes, A. Matrone, P. Lastella et al., “A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells,” Cell Death and Differentiation, vol. 14, no. 4, pp. 693–702, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Simone, “Signal-dependent control of autophagy and cell death in colorectal cancer cell: the role of the p38 pathway,” Autophagy, vol. 3, no. 5, pp. 468–471, 2007. View at Google Scholar · View at Scopus
  68. F. Chiacchiera, A. Matrone, E. Ferrari et al., “p38α blockade inhibits colorectal cancer growth in vivo by inducing a switch from HIF1α- to FoxO-dependent transcription,” Cell Death and Differentiation, vol. 16, no. 9, pp. 1203–1214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. F. Chiacchiera and C. Simone, “Inhibition of p38α unveils an AMPK-FoxO3A axis linking autophagy to cancer-specific metabolism,” Autophagy, vol. 5, no. 7, pp. 1030–1033, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. A. Matrone, V. Grossi, F. Chiacchiera et al., “P38α is required for ovarian cancer cell metabolism and survival,” International Journal of Gynecological Cancer, vol. 20, no. 2, pp. 203–211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Y. Yang, A. Miah, K. M. Sales, B. Fuller, A. M. Seifalian, and M. Winslet, “Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment,” International Journal of Oncology, vol. 38, no. 6, pp. 1695–1702, 2011. View at Publisher · View at Google Scholar
  72. S. Paillas, F. Boissière, F. Bibeau et al., “Targeting the p38 MAPK pathway inhibits irinotecan resistance in colon adenocarcinoma,” Cancer Research, vol. 71, no. 3, pp. 1041–1049, 2011. View at Publisher · View at Google Scholar
  73. E. F. Wagner and A. R. Nebreda, “Signal integration by JNK and p38 MAPK pathways in cancer development,” Nature Reviews Cancer, vol. 9, no. 8, pp. 537–549, 2009. View at Publisher · View at Google Scholar · View at Scopus