Assessment of p53 gene transfer and biological activities in a clinical study of adenovirus-p53 gene therapy for recurrent ovarian cancer

Wen, Sijian; Mahavni, Vikas; Quijano, Erlinda; Shinoda, Jeremy; Grace, Michael J.; Musco-Hobkinson, Mary Lynn; Yang, Tong‐Yuan; Chen, Yuetian; Runnenbaum, Ingo; Horowitz, JoAnn; Maneval, Dan; Hutchins, Beth; Buller, Richard E.

doi:10.1038/sj.cgt.7700562

Cited by 38 publications

(22 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene therapy based on the introduction of wild-type p53 (reviewed by Wen et al, 2003) and elimination of mutantp53-expressing cells (reviewed by Post, 2002) is undergoing clinical trials. Restoration of wild-type conformation to structurally contorted p53 DNA-binding mutants has been demonstrated, using peptide constructs and small molecular weight synthetic molecules (reviewed by Bullock and Fersht, 2001).…”

Section: P53-mediated Cancer Therapymentioning

confidence: 99%

Apoptosis - the p53 network

Haupt¹,

Berger²,

Goldberg³

et al. 2003

Journal of Cell Science

1,030

764

View full text Add to dashboard Cite

Exposure to cellular stress can trigger the p53 tumor suppressor, a sequence-specific transcription factor, to induce cell growth arrest or apoptosis. The choice between these cellular responses is influenced by many factors, including the type of cell and stress, and the action of p53 co-activators. p53 stimulates a wide network of signals that act through two major apoptotic pathways. The extrinsic, death receptor pathway triggers the activation of a caspase cascade, and the intrinsic, mitochondrial pathway shifts the balance in the Bcl-2 family towards the pro-apoptotic members, promoting the formation of the apoptosome, and consequently caspase-mediated apoptosis. The impact of these two apoptotic pathways may be enhanced when they converge through Bid, which is a p53 target. The majority of these apoptotic effects are mediated through the induction of specific apoptotic target genes. However, p53 can also promote apoptosis by a transcription-independent mechanism under certain conditions. Thus, a multitude of mechanisms are employed by p53 to ensure efficient induction of apoptosis in a stage-, tissue- and stress-signal-specific manner. Manipulation of the apoptotic functions of p53 constitutes an attractive target for cancer therapy.

show abstract

Section: P53-mediated Cancer Therapymentioning

confidence: 99%

Apoptosis - the p53 network

Haupt¹,

Berger²,

Goldberg³

et al. 2003

Journal of Cell Science

1,030

764

View full text Add to dashboard Cite

show abstract

“…39,133 The exogenous p53 functions both in ex vivo cell death induction and in vivo tumor suppression. In clinical trials, 124,130 adenovirus-mediated p53 gene therapy has been carried out in patients with head and neck, lung or ovarian cancers. Intratumoral or intraperitoneal administration of high titer adenoviruses carrying p53 proved to be safe with no significant toxicity observed even in repeated subsequent injections.…”

Section: Restoring and Enhancing P53 Function For Cancer Therapymentioning

confidence: 99%

Restoring p53-Dependent Tumor Suppression

Wang¹,

Rastinejad²,

El‐Deiry³

2003

Cancer Biology & Therapy

View full text Add to dashboard Cite

ABSTRACTp53 represents an ideal target for anti-cancer drug design, because p53 is mutated in more than half of human tumors. Most of the remaining tumors, although carrying wild-type p53, have defects in the p53-mediated apoptotic pathway. Activation of p53 activity by either chemotherapy or radiotherapy induces p53-dependent apoptosis in tumor cells with wild-type p53. Supplying exogenous wild-type p53 in cancer cells by gene delivery is effective in suppressing tumor growth of both mutant and wild-type p53-containing tumors. Blockage of p53 degradation pathways either by overexpression of ARF or interruption of MDM2:p53 interaction is effective in inducing p53 triggered tumor cell death. Since unlike most other tumor suppressor genes, mutant p53 is over expressed in tumor cells, a promising approach involves restoring tumor-suppressing function to mutant p53.

show abstract

“…Recently, gene therapy has become a promising new therapeutic option in the treatment of ovarian cancer, and is currently under intensive clinical investigation utilizing a variety of transgenes. [1][2] In addition to selection of therapeutic genes, the choice of an effective gene delivery vector is crucial for the success of this strategy. Adenovirus type 5-based vector (Ad5) is mostly favored over other vector systems because of its high gene transfer efficacy and high titer production.…”

Section: Introductionmentioning

confidence: 99%