Login Register Cart 0
Review Article

Applications of Recombinant Adenovirus-p53 Gene Therapy for Cancers in the Clinic in China

Author(s): Yu Xia, Xiuqin Li* and Wei Sun

Volume 20, Issue 2, 2020

Page: [127 - 141] Pages: 15

DOI: 10.2174/1566523220999200731003206

Price: $65

Abstract

Suppression of TP53 function is nearly ubiquitous in human cancers, and a significant fraction of cancers have mutations in the TP53 gene itself. Therefore, the wild-type TP53 gene has become an important target gene for transformation research of cancer gene therapy. In 2003, the first anti-tumor gene therapy drug rAd-p53 (recombinant human p53 adenovirus), trade name Gendicine™, was approved by the China Food and Drug Administration (CFDA) for treatment of head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy. The recombinant human TP53 gene is delivered into cancer cells by an adenovirus vector constructed to express the functional p53 protein. Although the only currently approved used of Gendicine is in combination with radiotherapy for treatment of HNSCC, clinical studies have been carried out for more than 20 other applications of Gendicine in treating cancer, including treatment of advanced lung cancer, advanced liver cancer, malignant gynecological tumors, and soft tissue sarcomas. Currently more than 30,000 patients have been treated with Gendicine. This review provides an overview of the clinical applications of Gendicine in China. We summarize a total of 48 studies with 2,561 patients with solid tumors, including 34 controlled clinical studies and 14 open clinical studies, i.e., clinical studies without a control group. There are 11 studies for head and neck cancer, 10 for liver cancer, 6 for malignant gynecological tumors, 4 for non-small cell lung cancer, 4 for soft tissue sarcoma, 4 for malignant effusion, 2 for gastrointestinal tumors, and 7 for other types of cancer. In all the reported clinical studies, the most common side effect was self-limited fever. Intratumoral injection and intra-arterial infusion were the most common routes of administration. Overall, Gendicine combined with chemotherapy, radiotherapy, or other conventional treatment regimens demonstrated significantly higher response rates compared to standard therapies alone. Some of the published studies also showed that Gendicine combination regimens demonstrated longer progression-free survival times than conventional treatments alone. To date, Gendicine has been clinically used in China for treatment of cancers other than HNSCC for more than ten years, mainly for patients with advanced or unresectable malignant tumors. However, the establishment of standard treatment regimens using TP53 gene therapy is still needed in order to advance its use in clinical practice.

Keywords: TP53, gendicine, recombinant adenovirus p53, China, gene therapy, clinical practice.

« Previous Next »
Graphical Abstract

[1]
World Health Organization Available at:. https://www.who.int/health-topics/cancer
[2]
Loponte S, Lovisa S, Deem AK, Carugo A, Viale A. The many facets of tumor heterogeneity: is metabolism lagging behind? Cancers (Basel) 2019; 11(10): 11.
[http://dx.doi.org/10.3390/cancers11101574] [PMID: 31623133]
[3]
Roth JA, Cristiano RJ. Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997; 89(1): 21-39.
[http://dx.doi.org/10.1093/jnci/89.1.21] [PMID: 8978404]
[4]
Brenner MK, Gottschalk S, Leen AM, Vera JF. Is cancer gene therapy an empty suit? Lancet Oncol 2013; 14(11): e447-56.
[http://dx.doi.org/10.1016/S1470-2045(13)70173-6] [PMID: 24079872]
[5]
Ma CC, Wang ZL, Xu T, He ZY, Wei YQ. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv 2020; 40107502
[http://dx.doi.org/10.1016/j.biotechadv.2019.107502] [PMID: 31887345]
[6]
Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 2009; 9(12): 862-73.
[http://dx.doi.org/10.1038/nrc2763] [PMID: 19935675]
[7]
Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502(7471): 333-9.
[http://dx.doi.org/10.1038/nature12634] [PMID: 24132290]
[8]
Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2(1)a001008
[http://dx.doi.org/10.1101/cshperspect.a001008] [PMID: 20182602]
[9]
Soussi T, Béroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer 2001; 1(3): 233-40.
[http://dx.doi.org/10.1038/35106009] [PMID: 11902578]
[10]
Shiraishi K, Kato S, Han SY, et al. Isolation of temperature-sensitive p53 mutations from a comprehensive missense mutation library. J Biol Chem 2004; 279(1): 348-55.
[http://dx.doi.org/10.1074/jbc.M310815200] [PMID: 14559903]
[11]
Isobe T, Hiyama K, Yoshida Y, Fujiwara Y, Yamakido M. Prognostic significance of p53 and ras gene abnormalities in lung adenocarcinoma patients with stage I disease after curative resection. Jpn J Cancer Res 1994; 85(12): 1240-6.
[http://dx.doi.org/10.1111/j.1349-7006.1994.tb02936.x] [PMID: 7852188]
[12]
Quinlan DC, Davidson AG, Summers CL, Warden HE, Doshi HM. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res 1992; 52(17): 4828-31.
[PMID: 1324796]
[13]
Martin HM, Filipe MI, Morris RW, Lane DP, Silvestre F. p53 expression and prognosis in gastric carcinoma. Int J Cancer 1992; 50(6): 859-62.
[http://dx.doi.org/10.1002/ijc.2910500604] [PMID: 1555884]
[14]
Hussain SP, Harris CC. Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res 1998; 58(18): 4023-37.
[PMID: 9751603]
[15]
Béroud C, Soussi T. The UMD-p53 database: new mutations and analysis tools. Hum Mutat 2003; 21(3): 176-81.
[http://dx.doi.org/10.1002/humu.10187] [PMID: 12619103]
[16]
Munro AJ, Lain S, Lane DP. P53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer 2005; 92(3): 434-44.
[http://dx.doi.org/10.1038/sj.bjc.6602358] [PMID: 15668707]
[17]
Bassett EA, Wang W, Rastinejad F, El-Deiry WS. Structural and functional basis for therapeutic modulation of p53 signaling. Clin Cancer Res 2008; 14(20): 6376-86.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1526] [PMID: 18927276]
[18]
Martins CP, Brown-Swigart L, Evan GI. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127(7): 1323-34.
[http://dx.doi.org/10.1016/j.cell.2006.12.007] [PMID: 17182091]
[19]
Zhang WW, Li L, Li D, et al. The first approved gene therapy product for cancer ad-p53 (gendicine): 12 years in the clinic. Hum Gene Ther 2018; 29(2): 160-79.
[http://dx.doi.org/10.1089/hum.2017.218] [PMID: 29338444]
[20]
Pearson S, Jia H, Kandachi K. China approves first gene therapy. Nat Biotechnol 2004; 22(1): 3-4.
[http://dx.doi.org/10.1038/nbt0104-3] [PMID: 14704685]
[21]
Peng Z. Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther 2005; 16(9): 1016-27.
[http://dx.doi.org/10.1089/hum.2005.16.1016] [PMID: 16149900]
[22]
Wilson JM. Gendicine: the first commercial gene therapy product. Hum Gene Ther 2005; 16(9): 1014-5.
[http://dx.doi.org/10.1089/hum.2005.16.1014] [PMID: 16149899]
[23]
Guo W, Song H. Development of gene therapeutics for head and neck cancer in china: from bench to bedside. Hum Gene Ther 2018; 29(2): 180-7.
[http://dx.doi.org/10.1089/hum.2017.230] [PMID: 29334764]
[24]
Xin H. Chinese gene therapy. Gendicine’s efficacy: hard to translate. Science 2006; 314(5803): 1233.
[http://dx.doi.org/10.1126/science.314.5803.1233] [PMID: 17124301]
[25]
Guo J, Xin H. Chinese gene therapy. Splicing out the West? Science 2006; 314(5803): 1232-5.
[http://dx.doi.org/10.1126/science.314.5803.1232] [PMID: 17124300]
[26]
Han DM, Huang ZG, Zhang W, et al. Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: phase I clinical trial and follow up. Zhonghua Yi Xue Za Zhi 2003; 83(23): 2029-32.
[PMID: 14703409]
[27]
Zhang SW, Xiao SW, Liu CQ, et al. Treatment of head and neck squamous cell carcinoma by recombinant adenovirus-p53 combined with radiotherapy: a phase II clinical trial of 42 cases. Zhonghua Yi Xue Za Zhi 2003; 83(23): 2023-8.
[PMID: 14703408]
[28]
Chen CB, Pan JJ, Xu LY. Recombinant adenovirus p53 agent injection combined with radiotherapy in treatment of nasopharyngeal carcinoma: a phase II clinical trial. Zhonghua Yi Xue Za Zhi 2003; 83(23): 2033-5.
[PMID: 14703410]
[29]
Zhang SW, Xiao SW, Liu CQ, et al. Recombinant adenovirus-p53 gene therapy combined with radiotherapy for head and neck squamous-cell carcinoma. Zhonghua Zhong Liu Za Zhi 2005; 27(7): 426-8.
[PMID: 16188130]
[30]
Pan JJ, Zhang SW, Chen CB, et al. Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma. J Clin Oncol 2009; 27(5): 799-804.
[http://dx.doi.org/10.1200/JCO.2008.18.9670] [PMID: 19103729]
[31]
Li Y, Li LJ, Wang LJ, et al. Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial. BMC Med 2014; 12: 16.
[http://dx.doi.org/10.1186/1741-7015-12-16] [PMID: 24479409]
[32]
Ma WS, Ma JG, Xing LN. Efficacy and safety of recombinant human adenovirus p53 combined with chemoradiotherapy in the treatment of recurrent nasopharyngeal carcinoma. Anticancer Drugs 2017; 28(2): 230-6.
[http://dx.doi.org/10.1097/CAD.0000000000000448] [PMID: 27775992]
[33]
Zhang S, Xiao S, Sun Y, et al. Clinical trial of recombinant adenovirus-p53 (Gendicine) combined with radiotherapy in nasopharyngeal carcinoma patients. Mol Ther 2006; 13: S280.
[http://dx.doi.org/10.1016/j.ymthe.2006.08.806]
[34]
Rong-rong L, Chang–you J, Ji-chuan C. Clinical effect of recombinant human p53 adv injection (Gendicine) in combination with radiotherapy in patients suffering from recurrent nasopharyngeal carcinoma. Shandong Daxue Er-Bi-Hou-Yan Xuebao 2010; 24: 13-6.
[35]
Si YF, He CC, Lan GP. Recombinant adenovirus p53 agent injection combined with radiotherapy and chemotherapy for intermediate and advanced stage nasopharyngeal carcinoma. Chin J Clin Oncol 2009; 36: 1031-9.
[http://dx.doi.org/10.3969/j.issn.1000-8179.2009.18.004]
[36]
Wang X, Wang J, Zhang J. Clinical observations of recombinant adenovirus-p53 combined with radiotherapy on nasopharyngeal squamous carcinoma. Mod J Int Tradit Chin West Med 2012; 21: 924-34.
[37]
Liu S, Chen P, Hu M, et al. Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer. Cancer Gene Ther 2013; 20(6): 375-8.
[http://dx.doi.org/10.1038/cgt.2013.30] [PMID: 23722592]
[38]
Li L, Huang Y, Wang L, et al. A Combination therapy of selective intraarterial gendicine infusion with chemotherapy for locally advanced head and neck carcinoma. Mol Ther 2006; 13: S20.
[http://dx.doi.org/10.1016/j.ymthe.2006.08.061]
[39]
Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474: 609-15.
[http://dx.doi.org/10.1038/nature10166]
[40]
Labidi-Galy SI, Papp E, Hallberg D, et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun 2017; 8(1): 1093.
[http://dx.doi.org/10.1038/s41467-017-00962-1] [PMID: 29061967]
[41]
Ahmed AA, Etemadmoghadam D, Temple J, et al. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol 2010; 221(1): 49-56.
[http://dx.doi.org/10.1002/path.2696] [PMID: 20229506]
[42]
Patch AM, Christie EL, Etemadmoghadam D, et al. Australian ovarian cancer study group. Whole-genome characterization of chemoresistant ovarian cancer. Nature 2015; 521(7553): 489-94.
[http://dx.doi.org/10.1038/nature14410] [PMID: 26017449]
[43]
Cole AJ, Dwight T, Gill AJ, et al. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing. Sci Rep 2016; 6: 26191.
[http://dx.doi.org/10.1038/srep26191] [PMID: 27189670]
[44]
Vang R, Levine DA, Soslow RA, Zaloudek C, Shih IeM, Kurman RJ. Molecular alterations of TP53 are a defining feature of ovarian high-grade serous carcinoma: a rereview of cases lacking tp53 mutations in the cancer genome atlas ovarian study. Int J Gynecol Pathol 2016; 35(1): 48-55.
[http://dx.doi.org/10.1097/PGP.0000000000000207] [PMID: 26166714]
[45]
Cui H, Guan C, Liu Q, Li L. Outcome of patients with recurrent epithelial ovarian carcinoma following treatment with recombinant human adenovirus p53 combined with chemotherapy. Zhongguo Zhongliu Shengwu Zhiliao Zazhi 2014; 21: 450-4.
[http://dx.doi.org/10.3872/j.issn.1007-385X.2014.04.016]
[46]
Su X, Chen WJ, Xiao SW, et al. Effect and safety of recombinant adenovirus-p53 transfer combined with radiotherapy on long-term survival of locally advanced cervical cancer. Hum Gene Ther 2016; 27(12): 1008-14.
[http://dx.doi.org/10.1089/hum.2016.043] [PMID: 27575731]
[47]
Xiao J, Zhou J, Fu M, et al. Efficacy of recombinant human adenovirus-p53 combined with chemotherapy for locally advanced cervical cancer: A clinical trial. Oncol Lett 2017; 13(5): 3676-80.
[http://dx.doi.org/10.3892/ol.2017.5901] [PMID: 28529585]
[48]
Xu Z, Quan X, Jiang J. Clinical observations of intensity modulated radiation therapy combined with recombinant human p53 adenovirus injection on middle-late type giant piece of cervical carcinoma. Anhui Med J 2015; 36: 19-22.
[49]
Zhang S. Recombinant adenovirus-p53 (rAd-p53) in combination with radiotherapy for treating cervical cancer. J Clin Oncol 2011; 29: 5096.
[http://dx.doi.org/10.1200/jco.2011.29.15_suppl.5096]
[50]
Xia Y, Du Z, Wang X, Li X. Treatment of Uterine Sarcoma with rAd-p53 (Gendicine) Followed by Chemotherapy: Clinical Study of TP53 Gene Therapy. Hum Gene Ther 2018; 29(2): 242-50.
[http://dx.doi.org/10.1089/hum.2017.206] [PMID: 29281902]
[51]
Xia Y, Wang L, Ma X, Li X. Investigation on the genomic characterization of uterine sarcoma for rAd-p53 combined with chemotherapy treatment. Hum Gene Ther 2020; 31(15-16): 881-90.
[http://dx.doi.org/10.1089/hum.2019.305] [PMID: 32013587]
[52]
Guan YS, Liu Y, Zou Q, et al. Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up. J Zhejiang Univ Sci B 2009; 10(5): 331-40.
[http://dx.doi.org/10.1631/jzus.B0820248] [PMID: 19434759]
[53]
Yang J, Wang X, Zheng G. A primary report of recombinant adeno-viral human p53 gene (rAd-p53) in combination with concurrent radio-chemotherapy in patients with T4N0-2M0 stage non-small cell lung cancer in elderly. Chin J Coal Ind Med 2013; 16: 1586-9.
[54]
Liu Y. Safety and short-term efficacy of advanced malignant cancer by Gendicine combined with chemotherapy. J Qiqihar Univ Med 2015; 36: 16-8.
[55]
Yang ZX, Wang D, Wang G, et al. Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma. J Cancer Res Clin Oncol 2010; 136(4): 625-30.
[http://dx.doi.org/10.1007/s00432-009-0701-6] [PMID: 19882171]
[56]
Guan YS, Liu Y, He Q, et al. p53 gene therapy in combination with transcatheter arterial chemoembolization for HCC: one-year follow-up. World J Gastroenterol 2011; 17(16): 2143-9.
[http://dx.doi.org/10.3748/wjg.v17.i16.2143] [PMID: 21547136]
[57]
Chen S, Chen J, Xi W, Xu W, Yin G. Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma. Am J Clin Oncol 2014; 37(1): 24-9.
[http://dx.doi.org/10.1097/COC.0b013e3181fe4688] [PMID: 24457472]
[58]
Tian G, Liu J, Zhou JS, Chen W. Multiple hepatic arterial injections of recombinant adenovirus p53 and 5-fluorouracil after transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a pilot phase II trial. Anticancer Drugs 2009; 20(5): 389-95.
[http://dx.doi.org/10.1097/CAD.0b013e32832a2df9] [PMID: 19287305]
[59]
Ou S-Q, Ma Y-L, Kang P, Li Z-K. Recombinant adenovirus-p53 gene therapy combined with transcatheter arterial chemoembolization for p53-positive and p53-negative hepatocellular carcinoma. Chinese J Interv Imag Ther 2010; 7: 354-7.
[60]
Shi S, Dong X, He W. Clinical study of P53 gene therapy on primary hepatocarcinoma. Mod J Int Tradit Chin West Med 2012; 10: 1036-7.
[61]
Feng X. Gendicine in interventional chemotherapy of primary hepatocarcinoma. World Chin J Digestology 2013; 21: 1437-41.
[http://dx.doi.org/10.11569/wcjd.v21.i15.1437]
[62]
Yu M, Chen W, Zhang J. p53 gene therapy for pulmonary metastasis tumor from hepatocellular carcinoma. Anticancer Drugs 2010; 21(9): 882-4.
[http://dx.doi.org/10.1097/CAD.0b013e32833db1bb] [PMID: 20679889]
[63]
Zhou J, Zhang Y, Zhao G, et al. The preliminary study of recombinant adenovirus p53 combined with transarterial embolization with particles for advanced hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi 2014; 94(9): 660-3.
[PMID: 24842203]
[64]
Shi S, Cui S, Hu W. Observation of curative effect of combination P53 gene therapy drug with Traditional Chinese Medicine on primary hepatocellular carcinoma Mod J Int Tradit Chin West Med 2012; 693-4
[65]
Lu P, Yang X, Huang Y, et al. Antitumor activity of a combination of rAd2p53 adenoviral gene therapy and radiotherapy in esophageal carcinoma. Cell Biochem Biophys 2011; 59(3): 147-52.
[http://dx.doi.org/10.1007/s12013-010-9122-z] [PMID: 21350839]
[66]
Dong M, Li X, Hong LJ, et al. Advanced malignant pleural or peritoneal effusion in patients treated with recombinant adenovirus p53 injection plus cisplatin. J Int Med Res 2008; 36(6): 1273-8.
[http://dx.doi.org/10.1177/147323000803600614] [PMID: 19094436]
[67]
Zhao WZ, Wang JK, Li W, et al. Clinical research on recombinant human Ad-p53 injection combined with cisplatin in treatment of malignant pleural effusion induced by lung cancer. Chin J Cancer 2009; 28: 1324-7.
[http://dx.doi.org/10.5732/cjc.009.10149]
[68]
Wang H, Zhao L, Zhang J. rAd-p53 combined with chemotherapy and local thermotherapy for patients with malignant serosal cavity effusion. China Cancer 2012; 21: 717-2.
[69]
Chen P. HU ZH, Zhang MH. Effects of recombinant adenovirus p53 injection on malignant pleural effusion. Med J West China 2010; 635-6
[70]
Li X, Xiao S, Li Y, Zhang S. Clinical antiangiogenic effect of recombinant adenovirus-p53 combined with hyperthermia for advanced cancer. Chin J Cancer Res 2013; 25(6): 749-55.
[PMID: 24385704]
[71]
Xiao SW, Xu YZ, Xiao BF, et al. Recombinant adenovirus-p53 gene therapy for advanced unresectable soft-tissue sarcomas. Hum Gene Ther 2018; 29(6): 699-707.
[http://dx.doi.org/10.1089/hum.2017.103] [PMID: 29284287]
[72]
Li JL, Cai Y, Zhang SW, et al. Combination of recombinant adenovirus-p53 with radiochemotherapy in unresectable pancreatic carcinoma. Chin J Cancer Res 2011; 23(3): 194-200.
[http://dx.doi.org/10.1007/s11670-011-0194-0] [PMID: 23467436]
[73]
Qi X, Yang Z, Han D, et al. The clinical effect of recombinant human Ad.p53 agent-Gendicine in advanced cancer patients. J Modern Oncol 2006; 14: 1295-7.
[74]
Zhu JX, Li ZM, Geng FY, et al. Treatment of recurrent malignant gliomas by surgery combined with recombinant adenovirus-p53 injection. Zhonghua Zhong Liu Za Zhi 2010; 32(9): 709-12.
[PMID: 21122390]
[75]
Zhu J. Preoperative recombinant adeno-viral human p53 gene (rAd-p53) therapy in treatment of locally advanced locally advanced papillary thyroid cancer (PTC) and folliculary thyroid cancer (FTC). J Clin Oncol 2011; 29: 5583-3.
[http://dx.doi.org/10.1200/jco.2011.29.15_suppl.5583]
[76]
Zhang Z. Recombinant adeno-viral human p53 gene combined with FOLFOX4 in treatment of advanced colorectal cancer. J Clin Oncol 2011; 29e14133
[77]
Gang X, Xiao S, Liu C, et al. Clinical effect of recombinant adenovirus-p53 combined with hyperthermia for advanced soft tissue sarcoma. Sci Tech Rev 2013; 25: 749-55.
[78]
Xiao S, Liu C, Sun Y. Clinical observation of the effect of recombinant adenovirus-p53 plus radio-thermotherapy on soft tissue sarcoma. Chin J Clin Oncol 2007; 34: 65-7.
[79]
Geng J, Xiao S, Zhang S, et al. Clinical effectiveness of recombinant adenovirus-p53 combined with radiotherapy in advanced soft tissue sarcoma: a report of 37 cases. J Clin Oncol 2014; 32: e21514-4.
[http://dx.doi.org/10.1200/jco.2014.32.15_suppl.e21514]
[80]
Zhang S, Xu G, Liu C, et al. Clinical study of recombinant adenovirus-p53 (Adp53) combined with hyperthermia in advanced cancer (a report of 15 cases). Int J Hyperthermia 2005; 21(7): 631-6.
[http://dx.doi.org/10.1080/02656730500147868] [PMID: 16304714]
[81]
Rui C, Xiaojing T, Yue M. The recent clinical efficacy of recombinant human Ad-P53 agent gendicine combined chemotherapy in malignant tumor patients. J Clin Exp Med 2014; 13: 1326-9.
[82]
Bouaoun L, Sonkin D, Ardin M, et al. tp53 variations in human cancers: New lessons from the IARC tp53 database and genomics data. Hum Mutat 2016; 37(9): 865-76.
[http://dx.doi.org/10.1002/humu.23035] [PMID: 27328919]
[83]
Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002; 19(6): 607-14.
[http://dx.doi.org/10.1002/humu.10081] [PMID: 12007217]
[84]
Ognjanovic S, Olivier M, Bergemann TL, Hainaut P. Sarcomas in TP53 germline mutation carriers: a review of the IARC TP53 database. Cancer 2012; 118(5): 1387-96.
[http://dx.doi.org/10.1002/cncr.26390] [PMID: 21837677]
[85]
Chen F, Wang W, El-Deiry WS. Current strategies to target p53 in cancer. Biochem Pharmacol 2010; 80(5): 724-30.
[http://dx.doi.org/10.1016/j.bcp.2010.04.031] [PMID: 20450892]
[86]
Brady CA, Attardi LD. p53 at a glance. J Cell Sci 2010; 123(Pt 15): 2527-32.
[http://dx.doi.org/10.1242/jcs.064501] [PMID: 20940128]
[87]
Tang J, Di J, Cao H, Bai J, Zheng J. p53-mediated autophagic regulation: A prospective strategy for cancer therapy. Cancer Lett 2015; 363(2): 101-7.
[http://dx.doi.org/10.1016/j.canlet.2015.04.014] [PMID: 25896632]
[88]
Huang X, Zhang Y, Tang Y, et al. A novel PTEN/mutant p53/c-Myc/Bcl-XL axis mediates context-dependent oncogenic effects of PTEN with implications for cancer prognosis and therapy. Neoplasia 2013; 15(8): 952-65.
[http://dx.doi.org/10.1593/neo.13376] [PMID: 23908595]
[89]
Ali A, Shah AS, Ahmad A. Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells. Cancer Lett 2014; 354(1): 87-96.
[http://dx.doi.org/10.1016/j.canlet.2014.07.045] [PMID: 25111898]
[90]
Dong P, Karaayvaz M, Jia N, et al. Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene 2013; 32(27): 3286-95.
[http://dx.doi.org/10.1038/onc.2012.334] [PMID: 22847613]
[91]
Atema A, Chène P. The gain of function of the p53 mutant Asp281Gly is dependent on its ability to form tetramers. Cancer Lett 2002; 185(1): 103-9.
[http://dx.doi.org/10.1016/S0304-3835(02)00318-X] [PMID: 12142085]
[92]
Liu K, Ling S, Lin WC. TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73. Mol Cell Biol 2011; 31(22): 4464-81.
[http://dx.doi.org/10.1128/MCB.05574-11] [PMID: 21930790]
[93]
El-Hizawi S, Lagowski JP, Kulesz-Martin M, Albor A. Induction of gene amplification as a gain-of-function phenotype of mutant p53 proteins. Cancer Res 2002; 62(11): 3264-70.
[PMID: 12036943]
[94]
Matas D, Sigal A, Stambolsky P, et al. Integrity of the N-terminal transcription domain of p53 is required for mutant p53 interference with drug-induced apoptosis. EMBO J 2001; 20(15): 4163-72.
[http://dx.doi.org/10.1093/emboj/20.15.4163] [PMID: 11483519]
[95]
Di Agostino S, Strano S, Emiliozzi V, et al. Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation. Cancer Cell 2006; 10(3): 191-202.
[http://dx.doi.org/10.1016/j.ccr.2006.08.013] [PMID: 16959611]
[96]
Gaiddon C, Lokshin M, Ahn J, Zhang T, Prives C. A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol Cell Biol 2001; 21(5): 1874-87.
[http://dx.doi.org/10.1128/MCB.21.5.1874-1887.2001] [PMID: 11238924]
[97]
Murphy KL, Dennis AP, Rosen JM. A gain of function p53 mutant promotes both genomic instability and cell survival in a novel p53-null mammary epithelial cell model. FASEB J 2000; 14(14): 2291-302.
[http://dx.doi.org/10.1096/fj.00-0128com] [PMID: 11053251]
[98]
Song H, Hollstein M, Xu Y. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 2007; 9(5): 573-80.
[http://dx.doi.org/10.1038/ncb1571] [PMID: 17417627]
[99]
Caulin C, Nguyen T, Lang GA, et al. An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations. J Clin Invest 2007; 117(7): 1893-901.
[http://dx.doi.org/10.1172/JCI31721] [PMID: 17607363]
[100]
Hingorani SR, Wang L, Multani AS, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005; 7(5): 469-83.
[http://dx.doi.org/10.1016/j.ccr.2005.04.023] [PMID: 15894267]
[101]
Valenti F, Ganci F, Fontemaggi G, et al. Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression. Oncotarget 2015; 6(8): 5547-66.
[http://dx.doi.org/10.18632/oncotarget.2587] [PMID: 25650659]
[102]
Samassekou O, Bastien N, Lichtensztejn D, Yan J, Mai S, Drouin R. Different TP53 mutations are associated with specific chromosomal rearrangements, telomere length changes, and remodeling of the nuclear architecture of telomeres. Genes Chromosomes Cancer 2014; 53(11): 934-50.
[http://dx.doi.org/10.1002/gcc.22205] [PMID: 25059482]
[103]
Scian MJ, Stagliano KE, Deb D, et al. Tumor-derived p53 mutants induce oncogenesis by transactivating growth-promoting genes. Oncogene 2004; 23(25): 4430-43.
[http://dx.doi.org/10.1038/sj.onc.1207553] [PMID: 15077194]
[104]
Petitjean A, Mathe E, Kato S, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007; 28(6): 622-9.
[http://dx.doi.org/10.1002/humu.20495] [PMID: 17311302]
[105]
Weisz L, Oren M, Rotter V. Transcription regulation by mutant p53. Oncogene 2007; 26(15): 2202-11.
[http://dx.doi.org/10.1038/sj.onc.1210294] [PMID: 17401429]
[106]
Marin MC, Jost CA, Brooks LA, et al. A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet 2000; 25(1): 47-54.
[http://dx.doi.org/10.1038/75586] [PMID: 10802655]
[107]
Muller PA, Trinidad AG, Timpson P, et al. Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene 2013; 32(10): 1252-65.
[http://dx.doi.org/10.1038/onc.2012.148] [PMID: 22580601]
[108]
Dong P, Xu Z, Jia N, Li D, Feng Y. Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway. Mol Cancer 2009; 8: 103.
[http://dx.doi.org/10.1186/1476-4598-8-103] [PMID: 19917135]
[109]
Adorno M, Cordenonsi M, Montagner M, et al. A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 2009; 137(1): 87-98.
[http://dx.doi.org/10.1016/j.cell.2009.01.039] [PMID: 19345189]
[110]
Coffill CR, Muller PA, Oh HK, et al. Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion. EMBO Rep 2012; 13(7): 638-44.
[http://dx.doi.org/10.1038/embor.2012.74] [PMID: 22653443]
[111]
Muller PA, Caswell PT, Doyle B, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell 2009; 139(7): 1327-41.
[http://dx.doi.org/10.1016/j.cell.2009.11.026] [PMID: 20064378]
[112]
Noll JE, Jeffery J, Al-Ejeh F, et al. Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11. Oncogene 2012; 31(23): 2836-48.
[http://dx.doi.org/10.1038/onc.2011.456] [PMID: 21986947]
[113]
Yeudall WA, Vaughan CA, Miyazaki H, et al. Gain-of-function mutant p53 upregulates CXC chemokines and enhances cell migration. Carcinogenesis 2012; 33(2): 442-51.
[http://dx.doi.org/10.1093/carcin/bgr270] [PMID: 22114072]
[114]
Vaughan CA, Singh S, Windle B, et al. p53 mutants induce transcription of NF-κB2 in H1299 cells through CBP and STAT binding on the NF-κB2 promoter and gain of function activity. Arch Biochem Biophys 2012; 518(1): 79-88.
[http://dx.doi.org/10.1016/j.abb.2011.12.006] [PMID: 22198284]
[115]
Ji L, Xu J, Liu J, et al. Mutant p53 promotes tumor cell malignancy by both positive and negative regulation of the transforming growth factor β (TGF-β) pathway. J Biol Chem 2015; 290(18): 11729-40.
[http://dx.doi.org/10.1074/jbc.M115.639351] [PMID: 25767119]
[116]
Subramanian M, Francis P, Bilke S, et al. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis. Oncogene 2015; 34(9): 1094-104.
[http://dx.doi.org/10.1038/onc.2014.46] [PMID: 24662829]
[117]
Fontemaggi G, Dell’Orso S, Trisciuoglio D, et al. The execution of the transcriptional axis mutant p53, E2F1 and ID4 promotes tumor neo-angiogenesis. Nat Struct Mol Biol 2009; 16(10): 1086-93.
[http://dx.doi.org/10.1038/nsmb.1669] [PMID: 19783986]
[118]
Capponcelli S, Pedrini E, Cerone MA, et al. Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation. Hum Mutat 2005; 26(2): 94-103.
[http://dx.doi.org/10.1002/humu.20192] [PMID: 15977174]
[119]
Khromova NV, Kopnin PB, Stepanova EV, Agapova LS, Kopnin BP. p53 hot-spot mutants increase tumor vascularization via ROS-mediated activation of the HIF1/VEGF-A pathway. Cancer Lett 2009; 276(2): 143-51.
[http://dx.doi.org/10.1016/j.canlet.2008.10.049] [PMID: 19091459]
[120]
Pfister NT, Fomin V, Regunath K, et al. Mutant p53 cooperates with the SWI/SNF chromatin remodeling complex to regulate VEGFR2 in breast cancer cells. Genes Dev 2015; 29(12): 1298-315.
[http://dx.doi.org/10.1101/gad.263202.115] [PMID: 26080815]
[121]
Weisz L, Damalas A, Liontos M, et al. Mutant p53 enhances nuclear factor kappaB activation by tumor necrosis factor alpha in cancer cells. Cancer Res 2007; 67(6): 2396-401.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2425] [PMID: 17363555]
[122]
Cooks T, Pateras IS, Tarcic O, et al. Mutant p53 prolongs NF-κB activation and promotes chronic inflammation and inflammation-associated colorectal cancer. Cancer Cell 2013; 23(5): 634-46.
[http://dx.doi.org/10.1016/j.ccr.2013.03.022] [PMID: 23680148]
[123]
Di Minin G, Bellazzo A, Dal Ferro M, et al. Mutant p53 reprograms TNF signaling in cancer cells through interaction with the tumor suppressor DAB2IP. Mol Cell 2014; 56(5): 617-29.
[http://dx.doi.org/10.1016/j.molcel.2014.10.013] [PMID: 25454946]
[124]
Ubertini V, Norelli G, D’Arcangelo D, et al. Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist. Oncogene 2015; 34(19): 2493-504.
[http://dx.doi.org/10.1038/onc.2014.191] [PMID: 24998848]
[125]
Frank DK, Frederick MJ, Liu TJ, Clayman GL. Bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of human squamous cell carcinoma of the head and neck. Clin Cancer Res 1998; 4(10): 2521-8.
[PMID: 9796986]
[126]
Fujiwara T, Kataoka M, Tanaka N. Adenovirus-mediated p53 gene therapy for human cancer. Mol Urol 2000; 4(2): 51-4.
[http://dx.doi.org/10.1089/10915360050138585] [PMID: 12006242]
[127]
Bouvet M, Ellis LM, Nishizaki M, et al. Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer. Cancer Res 1998; 58(11): 2288-92.
[PMID: 9622060]
[128]
Ning X, Sun Z, Wang Y, et al. Docetaxel plus trans-tracheal injection of adenoviral-mediated p53 versus docetaxel alone in patients with previously treated non-small-cell lung cancer. Cancer Gene Ther 2011; 18(6): 444-9.
[http://dx.doi.org/10.1038/cgt.2011.15] [PMID: 21455255]

Rights & Permissions Print Cite
Article Metrics
77
4
World Hemophilia Day
© 2024 Bentham Science Publishers | Privacy Policy