<i>In vitro</i> and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-<i>p53</i> Injection for Oral Leukoplakia

Li, Yang; Li, Longjiang; Zhang, Songtao; Wang, Lijuan; Zhang, Zhuang; Gao, Ning; Zhang, Yuanyuan; Chen, Qianming

doi:10.1158/1078-0432.ccr-09-1296

Cited by 43 publications

(43 citation statements)

References 41 publications

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“…In the second study, Li et al evaluated 22 patients who received intralesional rAd-p53 (5 doses over 2 weeks) for OLK. 18 Mild adverse events were observed, including transient fever in 7 (32%) patients and flu-like symptoms in 2 (9%) patients. Patients were followed for 24 months, and over this time, 5 (23%) had complete regression, 11 (50%) had decreased size of lesions, 4 (18%) had no improvement, and 2 (9%) progressed to invasive squamous cell carcinoma.…”

Section: Adenoviral P53 Gene Therapymentioning

confidence: 97%

p53-based therapeutics for head and neck squamous cell carcinoma

et al. 2013

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Inactivation of the tumor suppressor p53 is a pathogenetic event in the development of head and neck squamous cell carcinoma (HNSCC). In the absence of functional wildtype p53, HNSCC cells have increased resistance to standard chemotherapeutics and radiation. Numerous approaches to restore p53 function in cancer cells have been developed over the past several decades. This review article focuses on viral approaches to deliver wildtype p53 to HNSCC cells, a designer virus that selectively eliminates mutant p53 HNSCC cells, and chemical approaches to reactivate p53 function in HNSCC cells. These promising studies provide evidence that p53 therapeutics may prove useful alone or in combination with conventional chemotherapy and/or radiation for the management of HNSCC patients.

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Section: Adenoviral P53 Gene Therapymentioning

confidence: 97%

p53-based therapeutics for head and neck squamous cell carcinoma

et al. 2013

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“…More recent efforts elucidated combination therapies of gendicine and epirubicin hydrochlorid (EPI) in gastric cancer [123], and combinatorial Ad-p53 and radiation regimens for patient diagnosed with advanced nasopharyngeal carcinomas [124]. These and addition studies assessing intraepithelial injections of Ad-p53 for the treatment of oral leukoplakia, a precancerous lesion of squamous cell carcinomas [125], and bronchoalveolar lavage of Ad-p53 in patients with bronchioalveolar cell lung carcinoma [126], pointed to tumor inhibitory effects of Ad-p53, in particular in combination with chemo- and radiation therapy, and warrant further, in-depth clinical assessment. Additional efforts have been directed toward the characterization of more advanced vector systems [127], most importantly of oncolytic, conditionally replicating adenoviruses (CRAs) that only replicate in p53-dysfunctional tumor cells [128–130].…”

Section: Targeting P53 Signaling For Cancer Therapymentioning

confidence: 99%

Targeting the p53 signaling pathway in cancer therapy – the promises, challenges and perils

Stegh¹

2012

Expert Opinion on Therapeutic Targets

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Introduction Research over the past three decades has identified p53 as a multifunctional transcription factor, which regulates the expression of >2,500 target genes. p53 impacts myriad, highly diverse cellular processes, including the maintenance of genomic stability and fidelity, metabolism, longevity, and represents one of the most important and extensively studied tumor suppressors. Activated by various stresses, foremost genotoxic damage, hypoxia, heat shock and oncogenic assault, p53 blocks cancer progression by provoking transient or permanent growth arrest, by enabling DNA repair or by advancing cellular death programs. This potent and versatile anti-cancer activity profile, together with genomic and mutational analyses documenting inactivation of p53 in more than 50% of human cancers, motivated drug development efforts to (re-) activate p53 in established tumors. Areas covered In this review the complexities of p53 signaling in cancer are summarized. Current strategies and challenges to restore p53’s tumor suppressive function in established tumors, i.e. adenoviral gene transfer and small molecules to activate p53, to inactivate p53 inhibitors and to restore wild type function of p53 mutant proteins are discussed. Expert opinion It is indubitable that p53 represents an attractive target for the development of anti-cancer therapies. Whether p53 is ‘druggable’, however, remains an area of active research and discussion, as p53 has pro-survival functions and chronic p53 activation accelerates aging, which may compromise the long-term homeostasis of an organism. Thus, the complex biology and dual functions of p53 in cancer prevention and age-related cellular responses pose significant challenges on the development of p53-targeting cancer therapies.

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“…The dosages in the previous clinical trials of rAd-p53 varied dramatically, from 1–4 × 1012 viral particles per site [8,22,24,25,26,27,28,29,30,31,32,33,34,35,36,37], which were calculated based on the tumor sizes, the medical direction, and the researchers’ personal experiences. Li et al reported that when the MOI was 100, rAd-p53 infection could effectively introduce an exogenous p53 gene into POE-9n cells, and decrease the toxicity and side effects of the adenovirus [62]. Based on the differences in the cells of the solid cancer from various organs, preclinical research on the effective infection titer for gene therapy should be conducted before the clinical trials.…”

Section: Clinical Issues and Experiences Of Gene Therapymentioning

confidence: 99%

Historical and Clinical Experiences of Gene Therapy for Solid Cancers in China

Gao

Zhang

et al. 2017

Genes

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Based on the theoretical and clinical development of modern medicines, gene therapy has been a promising treatment strategy for cancer and other diseases. The practice of gene therapy is nearly 27 years old, since the first authorized gene transfer study took place at the National Institute of Health in 1989. However, gene therapy was not readily adopted worldwide, until recently. Several gene therapy clinical trials have been carried out in China since 1998, and medical research in China has flourished. In this report, we review the history of gene therapy in China, focusing on treatment protocol, the administration cycle, dosage calculation, and the evaluation of therapeutic effects, in order to provide more information for the additional development of this promising treatment strategy.

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In vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Oral Leukoplakia

Cited by 43 publications

References 41 publications

p53-based therapeutics for head and neck squamous cell carcinoma

p53-based therapeutics for head and neck squamous cell carcinoma

Targeting the p53 signaling pathway in cancer therapy – the promises, challenges and perils

Historical and Clinical Experiences of Gene Therapy for Solid Cancers in China

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