p38MAPK and chemotherapy: We always need to hear both sides of the story

Frontiers in Cell and Developmental Biology

Volumn 4, Issue JUN, 2016, Pages

  García Cano, Jesús ^a   Roche, Olga ^a   Cimas, Francisco J ^a   Pascual Serra, Raquel ^a   Ortega Muelas, Marta ^a   Fernández Aroca, Diego M ^a   Sánchez Prieto, Ricardo ^a  

^a University of Castilla La Mancha   (Spain)

Author keywords

Cancer; Chemotherapy; P38MAPK; P38MAPK inhibitors; Resistance; Sensitivity; Targeted therapy

Indexed keywords

EID: 85024388106     PISSN: None     EISSN: 2296634X     Source Type: Journal    
DOI: 10.3389/fcell.2016.00069     Document Type: Short Survey

References (102)

1. Aceves-Luquero, C. I., Agarwal, A., Callejas-Valera, J. L., Arias-González, L., Esparís-Ogando, A., del Peso Ovalle, L., et al. (2009). ERK2, but Not ERK1, mediates acquired and 'De novo' resistance to imatinib mesylate: implication for CML therapy. PLoS ONE 4:e6124. doi: 10.1371/journal.pone.0006124
2. Alvarado-Kristensson, M., Melander, F., Leandersson, K., Rönnstrand, L., Wernstedt, C., and Andersson, T. (2004). p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils. J. Exp. Med. 199, 449-458. doi: 10.1084/jem.20031771
3. Baldari, S., Ubertini, V., Garufi, A., D'Orazi, G., and Bossi, G. (2015). Targeting MKK3 as a novel anticancer strategy: molecular mechanisms and therapeutical implications. Cell Death Dis. 6:e1621. doi: 10.1038/cddis.2014.591
4. Baldwin, R. M., Garratt-Lalonde, M., Parolin, D. A. E., Krzyzanowski, P. M., Andrade, M. A., and Lorimer, I. A. J. (2006). Protection of glioblastoma cells from Cisplatin cytotoxicity via protein kinase Ciota-mediated attenuation of p38 MAP kinase signalling. Oncogene 25, 2909-2919. doi: 10.1038/sj.onc.1209312
5. Brozovic, A., Fritz, G., Christmann, M., Zisowsky, J., Jaehde, U., Osmak, M., et al. (2004). Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by Cisplatin is attenuated in human carcinoma cells that acquired drug resistance. Int. J. Cancer J. Int. Cancer 112, 974-985. doi: 10.1002/ijc.20522
6. Brozovic, A., and Osmak, M. (2007). Activation of mitogen-activated protein kinases by Cisplatin and their role in Cisplatin-resistance. Cancer Lett. 251, 1-16. doi: 10.1016/j.canlet.2006.10.007
7. Bucur, O., Stancu, A. L., Goganau, I., Petrescu, S. M., Pennarun, B., Bertomeu, T., et al. (2013). Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells. PLoS ONE 8:e77390. doi: 10.1371/journal.pone.0077390
8. Cai, B., Chang, S. H., Becker, E. B. E., Bonni, A., and Xia, Z. (2006). p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J. Biol. Chem. 281, 25215-25222. doi: 10.1074/jbc.M512627200
9. Cerezo-Guisado, M. I., del Reino, P., Remy, G., Kuma, Y., Arthur, J. S. C., Gallego-Ortega, D., et al. (2011). Evidence of p38γ and p38d involvement in cell transformation processes. Carcinogenesis 32, 1093-1099. doi: 10.1093/carcin/bgr079
10. Cimas, F., Callejas-Valera, J., Pascual-Serra, R., García-Cano, J., García-Gil, E., de la Cruz Morcillo, M., et al. (2015). MKP1 mediates chemosensitizer effects of E1a in response to Cisplatin in non-small cell lung carcinoma cells. Oncotarget 6, 44095-44107. doi: 10.18632/oncotarget.6574
11. Clark, A. R., and Dean, J. L. (2012). The p38 MAPK pathway in rheumatoid arthritis: a sideways look. Open Rheumatol. J. 6, 209-219. doi: 10.2174/1874312901206010209
12. Comes, F., Matrone, A., Lastella, P., Nico, B., Susca, F. C., Bagnulo, R., et al. (2007). A novel cell type-specific role of p38alpha in the control of autophagy and cell death in colorectal cancer cells. Cell Death Differ. 14, 693-702. doi: 10.1038/sj.cdd.4402076
13. Corrêa, S. A. L., and Eales, K. L. (2012). The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. J. Signal Transduct. 2012:649079. doi: 10.1155/2012/649079
14. Cuadrado, A., Lafarga, V., Cheung, P. C. F., Dolado, I., Llanos, S., Cohen, P., et al. (2007). A new p38 MAP kinase-regulated transcriptional coactivator that stimulates p53-dependent apoptosis. EMBO J. 26, 2115-2126. doi: 10.1038/sj.emboj.7601657
15. de la Cruz-Morcillo, M. A., Valero, M. L. L., Callejas-Valera, J. L., Arias-González, L., Melgar-Rojas, P., Galán-Moya, E. M., et al. (2012). P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-Fluorouracil: implication in resistance. Oncogene 31, 1073-1085. doi: 10.1038/onc.2011.321
16. Del Reino, P., Alsina-Beauchamp, D., Escós, A., Cerezo-Guisado, M. I., Risco, A., Aparicio, N., et al. (2014). Pro-oncogenic role of alternative p38 mitogen-activated protein kinases p38γ and p38d, linking inflammation and cancer in colitis-associated colon cancer. Cancer Res. 74, 6150-6160. doi: 10.1158/0008-5472.CAN-14-0870
17. De Luca, A., Lamura, L., Gallo, M., Maffia, V., and Normanno, N. (2012). Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration. J. Cell. Biochem. 113, 3363-3370. doi: 10.1002/jcb.24212
18. Dienstmann, R., Markman, B., and Tabernero, J. (2012). Application of monoclonal antibodies as cancer therapy in solid tumours. Curr. Clin. Pharmacol. 7, 137-145. doi: 10.2174/157488412800228929
19. Dolado, I., Swat, A., Ajenjo, N., De Vita, G., Cuadrado, A., and Nebreda, A. R. (2007). p38alpha MAP kinase as a sensor of reactive oxygen species in tumourigenesis. Cancer Cell 11, 191-205. doi: 10.1016/j.ccr.2006.12.013
20. Donnelly, S. M., Paplomata, E., Peake, B. M., Sanabria, E., Chen, Z., and Nahta, R. (2014). P38 MAPK contributes to resistance and invasiveness of HER2-overexpressing breast cancer. Curr. Med. Chem. 21, 501-510. doi: 10.2174/0929867320666131119155023
21. Doshi, G., Sonpavde, G., and Sternberg, C. N. (2012). Clinical and pharmacokinetic evaluation of satraplatin. Expert Opin. Drug Metab. Toxicol. 8, 103-111. doi: 10.1517/17425255.2012.636352
22. Druker, B. J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G. M., Fanning, S., et al. (1996). Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566. doi: 10.1038/nm0596-561
23. Dumka, D., Puri, P., Carayol, N., Lumby, C., Balachandran, H., Schuster, K., et al. (2009). Activation of the p38 Map kinase pathway is essential for the antileukemic effects of dasatinib. Leuk. Lymphoma 50, 2017-2029. doi: 10.3109/10428190903147637
24. Elsea, C. R., Roberts, D. A., Druker, B. J., and Wood, L. J. (2008). Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-Fluorouracil, and doxorubicin without affecting tumouricidal activity. PLoS ONE 3:e2355. doi: 10.1371/journal.pone.0002355
25. Fram, R. J., and Kufe, D. W. (1982). DNA strand breaks caused by inhibitors of DNA synthesis: 1-ß-d-arabinofuranosylcytosine and aphidicolin. Cancer Res. 42, 4050-4053
26. Galan-Moya, E. M., de la Cruz-Morcillo, M. A., Llanos Valero, M., Callejas-Valera, J. L., Melgar-Rojas, P., Hernadez Losa, J., et al. (2011). Balance between MKK6 and MKK3 mediates p38 MAPK associated resistance to Cisplatin in NSCLC. PLoS ONE 6:e28406. doi: 10.1371/journal.pone.0028406
27. Galan-Moya, E. M., Hernandez-Losa, J., Aceves Luquero, C. I., de la Cruz-Morcillo, M. A., Ramírez-Castillejo, C., Callejas-Valera, J. L., et al. (2008). c-Abl activates p38 MAPK independently of its tyrosine kinase activity: implications in Cisplatin-based therapy. Int. J. Cancer J. Int. Cancer 122, 289-297. doi: 10.1002/ijc.23063
28. Gao, J., Gao, J., Qian, L., Wang, X., Wu, M., Zhang, Y., et al. (2014). Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-Fluorouracil. Cancer Biol. Ther. 15, 982-991. doi: 10.4161/cbt.29114
29. García-Cano, J., Ambroise, G., Pascual-Serra, R., Carrión, M. C., Serrano-Oviedo, L., Ortega-Muelas, M., et al. (2015). Exploiting the potential of autophagy in Cisplatin therapy: a new strategy to overcome resistance. Oncotarget 6, 15551-15565. doi: 10.18632/oncotarget.3902
30. Garcia-Manero, G., Khoury, H. J., Jabbour, E., Lancet, J., Winski, S. L., Cable, L., et al. (2015). A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 21, 985-994. doi: 10.1158/1078-0432.CCR-14-1765
31. Genovese, M. C., Cohen, S. B., Wofsy, D., Weinblatt, M. E., Firestein, G. S., Brahn, E., et al. (2011). A 24-week, randomized, double-blind, placebo-controlled, parallel group study of the efficacy of oral SCIO-469, a p38 mitogen-activated protein kinase inhibitor, in patients with active rheumatoid arthritis. J. Rheumatol. 38, 846-854. doi: 10.3899/jrheum.100602
32. Germani, A., Matrone, A., Grossi, V., Peserico, A., Sanese, P., Liuzzi, M., et al. (2014). Targeted therapy against chemoresistant colorectal cancers: inhibition of p38a modulates the effect of Cisplatin in vitro and in vivo through the tumour suppressor FoxO3A. Cancer Lett. 344, 110-118. doi: 10.1016/j.canlet.2013.10.035
33. Gesto, D. S., Cerqueira, N. M., and Fernandes, P. A, Ramos, M. J. (2012). Gemcitabine: a critical nucleoside for cancer therapy. Curr. Med. Chem. 19, 1076-1087. doi: 10.2174/092986712799320682
34. Grant, S., Freemerman, A. J., Birrer, M. J., Martin, H. A., Turner, A. J., Szabo, E., et al. (1996). Effect of 1-beta-D-arabinofuranosylcytosine on apoptosis and differentiation in human monocytic leukemia cells (U937) expressing a c-Jun dominant-negative mutant protein (TAM67). Cell Growth Differ. 7, 603
35. Gupta, J., del Barco Barrantes, I., Igea, A., Sakellariou, S., Pateras, I. S., Gorgoulis, V. G., et al. (2014). Dual function of p38a MAPK in colon cancer: suppression of colitis-associated tumour initiation but requirement for cancer cell survival. Cancer Cell 25, 484-500. doi: 10.1016/j.ccr.2014.02.019
36. Gupta, J., Igea, A., Papaioannou, M., Lopez-Casas, P. P., Llonch, E., Hidalgo, M., et al. (2015). Pharmacological inhibition of p38 MAPK reduces tumour growth in patient-derived xenografts from colon tumours. Oncotarget 6, 8539-8551. doi: 10.18632/oncotarget.3816
37. Hamilton, G., and Olszewski, U. (2013). Picoplatin pharmacokinetics and chemotherapy of non-small cell lung cancer. Expert Opin. Drug Metab. Toxicol. 9, 1381-1390. doi: 10.1517/17425255.2013.815724
38. Han, J., Lee, J. D., Bibbs, L., and Ulevitch, R. J. (1994). A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265, 808-811. doi: 10.1126/science.7914033
39. Henricks, L. M., Schellens, J. H. M., Huitema, A. D. R., and Beijnen, J. H. (2015). The use of combinations of monoclonal antibodies in clinical oncology. Cancer Treat. Rev. 41, 859-867. doi: 10.1016/j.ctrv.2015.10.008
40. Hernández Losa, J., Parada Cobo, C., Guinea Viniegra, J., Sánchez-Arevalo Lobo, V. J., Ramón y Cajal, S., and Sánchez-Prieto, R. (2003). Role of the p38 MAPK pathway in Cisplatin-based therapy. Oncogene 22, 3998-4006. doi: 10.1038/sj.onc.1206608
41. Höpfner, M., Sutter, A. P., Gerst, B., Zeitz, M., and Scherübl, H. (2003). A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839). Br. J. Cancer 89, 1766-1775. doi: 10.1038/sj.bjc.6601346
42. Hou, S., Suresh, P. S., Qi, X., Lepp, A., Mirza, S. P., and Chen, G. (2012). p38γ Mitogen-activated protein kinase signals through phosphorylating its phosphatase PTPH1 in regulating ras protein oncogenesis and stress response. J. Biol. Chem. 287, 27895-27905. doi: 10.1074/jbc.M111.335794
43. Igea, A., and Nebreda, A. R. (2015). The stress kinase p38a as a target for cancer therapy. Cancer Res. 75, 3997-4002. doi: 10.1158/0008-5472.CAN-15-0173
44. Jacquel, A., Colosetti, P., Grosso, S., Belhacene, N., Puissant, A., Marchetti, S., et al. (2007). Apoptosis and erythroid differentiation triggered by Bcr-Abl inhibitors in CML cell lines are fully distinguishable processes that exhibit different sensitivity to caspase inhibition. Oncogene 26, 2445-2458. doi: 10.1038/sj.onc.1210034
45. Jiang, T., Zhuang, J., Duan, H., Luo, Y., Zeng, Q., Fan, K., et al. (2012). CD146 is a coreceptor for VEGFR-2 in tumour angiogenesis. Blood 120, 2330-2339. doi: 10.1182/blood-2012-01-406108
46. Kang, D., Choi, H. J., Kang, S., Kim, S. Y., Hwang, Y., Je, S., et al. (2015). Ratio of phosphorylated HSP27 to nonphosphorylated HSP27 biphasically acts as a determinant of cellular fate in Gemcitabine-resistant pancreatic cancer cells. Cell. Signal. 27, 807-817. doi: 10.1016/j.cellsig.2015.01.007
47. Kao, Y.-T., Hsu, W.-C., Hu, H.-T., Hsu, S.-H., Lin, C.-S., Chiu, C.-C., et al. (2014). Involvement of p38 mitogen-activated protein kinase in acquired Gemcitabine-resistant human urothelial carcinoma sublines. Kaohsiung J. Med. Sci. 30, 323-330. doi: 10.1016/j.kjms.2014.03.004
48. Klotz, R., Zeimet, A. G., Reimer, D., Müller-Holzner, E., Chamson, M., and Marth, C. (2008). Activated p38-MAPK and gemcitabine sensitivity in recurrent ovarian cancer. Anticancer Res. 28, 2975-2980
49. Ko, J.-C., Chiu, H.-C., Wo, T.-Y., Huang, Y.-J., Tseng, S.-C., Huang, Y.-C., et al. (2013). Inhibition of p38 MAPK-dependent MutS homologue-2 (MSH2) expression by metformin enhances gefitinib-induced cytotoxicity in human squamous lung cancer cells. Lung Cancer Amst. Neth. 82, 397-406. doi: 10.1016/j.lungcan.2013.09.011
50. Kohmura, K., Miyakawa, Y., Kawai, Y., Ikeda, Y., and Kizaki, M. (2004). Different roles of p38 MAPK and ERK in STI571-induced multi-lineage differentiation of K562 cells. J. Cell. Physiol. 198, 370-376. doi: 10.1002/jcp.10426
51. Kokubo, Y., Gemma, A., Noro, R., Seike, M., Kataoka, K., Matsuda, K., et al. (2005). Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA). Br. J. Cancer 92, 1711-1719. doi: 10.1038/sj.bjc.6602559
52. Köpper, F., Bierwirth, C., Schön, M., Kunze, M., Elvers, I., Kranz, D., et al. (2013). Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity. Proc. Natl. Acad. Sci. U.S.A. 110, 16856-16861. doi: 10.1073/pnas.1304355110
53. Köpper, F., Binkowski, A. M., Bierwirth, C., and Dobbelstein, M. (2014). The MAPK-activated protein kinase 2 mediates Gemcitabine sensitivity in pancreatic cancer cells. Cell Cycle 13, 884-889. doi: 10.4161/cc.28292
54. Koul, H. K., Pal, M., and Koul, S. (2013). Role of p38 MAP kinase signal transduction in solid tumours. Genes Cancer 4, 342-359. doi: 10.1177/1947601913507951
55. Kragholm, K., Newby, L. K., and Melloni, C. (2015). Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod. Drug Des. Devel. Ther. 9, 4279-4286. doi: 10.2147/DDDT.S69546
56. Kyriakis, J. M., and Avruch, J. (2012). Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol. Rev. 92, 689-737. doi: 10.1152/physrev.00028.2011
57. Lalaoui, N., Hänggi, K., Brumatti, G., Chau, D., Nguyen, N.-Y. N., Vasilikos, L., et al. (2016). Targeting p38 or MK2 enhances the anti-leukemic activity of smac-mimetics. Cancer Cell 29, 145-158. doi: 10.1016/j.ccell.2016.01.006
58. Lee, J.-Y., Lee, Y.-M., Chang, G.-C., Yu, S.-L., Hsieh, W.-Y., Chen, J. J. W., et al. (2011). Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS ONE 6:e23756. doi: 10.1371/journal.pone.0023756
59. Liu, C.-L., Chen, S.-F., Wu, M.-Z., Jao, S.-W., Lin, Y.-S., Yang, C.-Y., et al. (2016). The molecular and clinical verification of therapeutic resistance via the p38 MAPK-Hsp27 axis in lung cancer. Oncotarget 7, 14279-14290. doi: 10.18632/oncotarget.7306
60. Liu, F., Gore, A. J., Wilson, J. L., and Korc, M. (2014). DUSP1 Is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine. PLoS ONE 9:e84982. doi: 10.1371/journal.pone.0084982
61. Longley, D. B., Harkin, D. P., and Johnston, P. G. (2003). 5-Fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330-338. doi: 10.1038/nrc1074
62. MacNee, W., Allan, R. J., Jones, I., De Salvo, M. C., and Tan, L. F. (2013). Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax 68, 738-745. doi: 10.1136/thoraxjnl-2012-202744
63. MacNeil, A. J., Jiao, S.-C., McEachern, L. A., Yang, Y. J., Dennis, A., Yu, H., et al. (2014). MAPK kinase 3 is a tumour suppressor with reduced copy number in breast cancer. Cancer Res. 74, 162-172. doi: 10.1158/0008-5472.CAN-13-1310
64. Maha, A., Cheong, S.-K., Leong, C.-F., and Seow, H.-F. (2009). Molecular responses during chemotherapy in acute myeloid leukemias in predicting poor-response to standard chemotherapy. Malays. J. Pathol. 31, 81-91
65. Major, P. P., Egan, E. M., Herrick, D. J., and Kufe, D. W. (1982). Effect of ara-C incorporation on deoxyribonucleic acid synthesis in cells. Biochem. Pharmacol. 31, 2937-2940. doi: 10.1016/0006-2952(82)90266-0
66. Mansouri, A., Ridgway, L. D., Korapati, A. L., Zhang, Q., Tian, L., Wang, Y., et al. (2003). Sustained activation of JNK/p38 MAPK pathways in response to Cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J. Biol. Chem. 278, 19245-19256. doi: 10.1074/jbc.M208134200
67. Mariadason, J. M., Arango, D., Shi, Q., Wilson, A. J., Corner, G. A., Nicholas, C., et al. (2003). Gene expression profiling-based prediction of response of colon carcinoma cells to 5-Fluorouracil and camptothecin. Cancer Res. 63, 8791-8812
68. Marks-Konczalik, J., Costa, M., Robertson, J., McKie, E., Yang, S., and Pascoe, S. (2015). A post-hoc subgroup analysis of data from a six month clinical trial comparing the efficacy and safety of losmapimod in moderate-severe COPD patients with = 2% and > 2% blood eosinophils. Respir. Med. 109, 860-869. doi: 10.1016/j.rmed.2015.05.003
69. Matsunaga, A., Ishii, Y., Tsuruta, M., Okabayashi, K., Hasegawa, H., and Kitagawa, Y. (2014). Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-Fluorouracil in colorectal cancer cells. Oncol. Lett. 8, 2496-2500. doi: 10.3892/ol.2014.2580
70. McLay, L. M., Halley, F., Souness, J. E., McKenna, J., Benning, V., Birrell, M., et al. (2001). The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy. Bioorg. Med. Chem. 9, 537-554. doi: 10.1016/S0968-0896(00)00331-X
71. Moon, D., Kim, M., Lee, J., Choi, Y., Lee, M., and Kim, G. (2007). Molecular mechanisms of ZD1839 (Iressa)-induced apoptosis in human leukemic U937 cells. Acta Pharmacol. Sin. 28, 1205-1214. doi: 10.1111/j.1745-7254.2007.00615.x
72. Nakashima, M., Adachi, S., Yasuda, I., Yamauchi, T., Kawaguchi, J., Itani, M., et al. (2011). Phosphorylation status of heat shock protein 27 plays a key role in Gemcitabine-induced apoptosis of pancreatic cancer cells. Cancer Lett. 313, 218-225. doi: 10.1016/j.canlet.2011.09.008
73. O'Callaghan, C., Fanning, L. J., and Barry, O. P. (2015). p38d MAPK phenotype: an indicator of chemotherapeutic response in oesophageal squamous cell carcinoma. Anticancer. Drugs 26, 46-55. doi: 10.1097/CAD.0000000000000156
74. O'Donoghue, M. L., Glaser, R., Aylward, P. E., Cavender, M. A., Crisp, A., Fox, K. A. A., et al. (2015). Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial. Am. Heart J. 169, 622-630.e6. doi: 10.1016/j.ahj.2015.02.012
75. Pandey, P., Raingeaud, J., Kaneki, M., Weichselbaum, R., Davis, R. J., Kufe, D., et al. (1996). Activation of p38 mitogen-activated protein kinase by c-Abl-dependent and-independent mechanisms. J. Biol. Chem. 271, 23775-23779. doi: 10.1074/jbc.271.39.23775
76. Parmar, S., Katsoulidis, E., Verma, A., Li, Y., Sassano, A., Lal, L., et al. (2004). Role of the p38 mitogen-activated protein kinase pathway in the generation of the effects of Imatinib mesylate (STI571) in BCR-ABL-expressing cells. J. Biol. Chem. 279, 25345-25352. doi: 10.1074/jbc.M400590200
77. Patnaik, A., Haluska, P., Tolcher, A. W., Erlichman, C., Papadopoulos, K. P., Lensing, J. L., et al. (2016). A first-in-human phase i study of the oral p38 MAPK inhibitor, ralimetinib (LY2228820 Dimesylate), in patients with advanced cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 22, 1095-1102. doi: 10.1158/1078-0432.CCR-15-1718
78. Pereira, L., Igea, A., Canovas, B., Dolado, I., and Nebreda, A. R. (2013). Inhibition of p38 MAPK sensitizes tumour cells to Cisplatin-induced apoptosis mediated by reactive oxygen species and JNK. EMBO Mol. Med. 5, 1759-1774. doi: 10.1002/emmm.201302732
79. Pignochino, Y., Dell'Aglio, C., Inghilleri, S., Zorzetto, M., Basiricò, M., Capozzi, F., et al. (2015). The combination of sorafenib and everolimus shows antitumour activity in preclinical models of malignant pleural mesothelioma. BMC Cancer 15:374. doi: 10.1186/s12885-015-1363-1
80. Pillaire, M. J., Nebreda, A. R., and Darbon, J. M. (2000). Cisplatin and UV radiation induce activation of the stress-activated protein kinase p38gamma in human melanoma cells. Biochem. Biophys. Res. Commun. 278, 724-728. doi: 10.1006/bbrc.2000.3877
81. Planchard, D., Camara-Clayette, V., Dorvault, N., Soria, J.-C., and Fouret, P. (2012). p38 Mitogen-activated protein kinase signalling, ERCC1 expression, and viability of lung cancer cells from never or light smoker patients. Cancer 118, 5015-5025. doi: 10.1002/cncr.27510
82. Pritchard, A. L., and Hayward, N. K. (2013). Molecular pathways: mitogen-activated protein kinase pathway mutations and drug resistance. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 19, 2301-2309. doi: 10.1158/1078-0432.CCR-12-0383
83. Rey, C., Faustin, B., Mahouche, I., Ruggieri, R., Brulard, C., Ichas, F., et al. (2015). The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer. Oncogene 35, 3190-3200. doi: 10.1038/onc.2015.379
84. Rudalska, R., Dauch, D., Longerich, T., McJunkin, K., Wuestefeld, T., Kang, T.-W., et al. (2014). In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer. Nat. Med. 20, 1138-1146. doi: 10.1038/nm.3679
85. Saleem, A., Datta, R., Yuan, Z. M., Kharbanda, S., and Kufe, D. (1995). Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents. Cell Growth Differ. 6, 1651
86. Sánchez-Arévalo Lobo, V. J., Aceves Luquero, C. I., álvarez-Vallina, L., Tipping, A. J., Viniegra, J. G., Hernández Losa, J., et al. (2005). Modulation of the p38 MAPK (mitogen-activated protein kinase) pathway through Bcr/Abl: implications in the cellular response to Ara-C. Biochem. J. 387, 231-238. doi: 10.1042/BJ20040927
87. Sanchez-Prieto, R., Rojas, J. M., Taya, Y., and Gutkind, J. S. (2000). A role for the p38 mitogen-acitvated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents. Cancer Res. 60, 2464-2472
88. Santoro, V., Jia, R., Thompson, H., Nijhuis, A., Jeffery, R., Kiakos, K., et al. (2015). Role of reactive oxygen species in the abrogation of oxaliplatin activity by cetuximab in colorectal cancer. J. Natl. Cancer Inst. 108:djv394. doi: 10.1093/jnci/djv394
89. Selness, S. R., Devraj, R. V., Devadas, B., Walker, J. K., Boehm, T. L., Durley, R. C., et al. (2011). Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase. Bioorg. Med. Chem. Lett. 21, 4066-4071. doi: 10.1016/j.bmcl.2011.04.121
90. Sheng, G., Guo, J., and Warner, B. W. (2007). Epidermal growth factor receptor signalling modulates apoptosis via p38alpha MAPK-dependent activation of Bax in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G599-G606. doi: 10.1152/ajpgi.00182.2007
91. Singh, D., Siew, L., Christensen, J., Plumb, J., Clarke, G. W., Greenaway, S., et al. (2015). Oral and inhaled p38 MAPK inhibitors: effects on inhaled LPS challenge in healthy subjects. Eur. J. Clin. Pharmacol. 71, 1175-1184. doi: 10.1007/s00228-015-1920-1
92. Stadheim, T. A., Saluta, G. R., and Kucera, G. L. (2000). Role of c-Jun N-terminal kinase/p38 stress signalling in 1-ß-d-arabinofuranosylcytosine-induced apoptosis. Biochem. Pharmacol. 59, 407-418. doi: 10.1016/S0006-2952(99)00330-5
93. St Germain, C., Niknejad, N., Ma, L., Garbuio, K., Hai, T., and Dimitroulakos, J. (2010). Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3. Neoplasia 12, 527-538. doi: 10.1593/neo.92048
94. Villar, V. H., Vögler, O., Martínez-Serra, J., Ramos, R., Calabuig-Fariñas, S., Gutiérrez, A., et al. (2012). Nilotinib counteracts p-glycoprotein-mediated multidrug resistance and synergizes the antitumoural effect of doxorubicin in soft tissue sarcomas. PLoS ONE 7:e37735. doi: 10.1371/journal.pone.0037735
95. Wagner, E. F., and Nebreda, A. R. (2009). Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer 9, 537-549. doi: 10.1038/nrc2694
96. Wilhelm, S. M., Adnane, L., Newell, P., Villanueva, A., Llovet, J. M., and Lynch, M. (2008). Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signalling. Mol. Cancer Ther. 7, 3129-3140. doi: 10.1158/1535-7163.MCT-08-0013
97. Wu, Y., Hiwasa, T., Isogai, E., Sonoda, T., Kita, K., Chen, Z., et al. (1998). Activation of MAP kinases by 5-Fluorouracil in a 5-Fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line. Int. J. Oncol. 13, 1241-1245. doi: 10.3892/ijo.13.6.1241
98. Yang, S. Y., Miah, A., Sales, K. M., Fuller, B., Seifalian, A. M., and Winslet, M. (2011). Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-Fluorouracil treatment. Int. J. Oncol. 38, 1695-1702. doi: 10.3892/ijo.2011.982
99. Yang, X., Wang, J., Dai, J., Shao, J., Ma, J., Chen, C., et al. (2015). Autophagy protects against dasatinib-induced hepatotoxicity via p38 signalling. Oncotarget 6, 6203-6217. doi: 10.18632/oncotarget.3357
100. Yong, K. J., Milenic, D. E., Baidoo, K. E., Kim, Y.-S., and Brechbiel, M. W. (2013). Gene expression profiling upon (212) Pb-TCMC-trastuzumab treatment in the LS-174T i.p. xenograft model. Cancer Med. 2, 646-653. doi: 10.1002/cam4.132
101. Zhao, H.-Y., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., et al. (2008). Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-Fluorouracil. Cancer Res. 68, 7035-7041. doi: 10.1158/0008-5472.CAN-07-6496
102. Zur, R., Garcia-Ibanez, L., Nunez-Buiza, A., Aparicio, N., Liappas, G., Escós, A., et al. (2015). Combined deletion of p38γ and p38d reduces skin inflammation and protects from carcinogenesis. Oncotarget 6, 12920-12935. doi: 10.18632/oncotarget.4320