Dataset Information

Targeting the P53 Protein for Cancer Therapies: The Translational Impact of P53 Research.

ABSTRACT: It is only recently that drugs targeting K-RAS and Tp53 missense mutations have been developed, and along with the allele specific nature of some of these drugs comes the possibility of combining them with the immunologic therapies for cancers. It has taken about 40 years since their discoveries to understand the pathways they command, how they function, and how they interact with the environment of the cells they control. This communication focuses on the transfer of some of the hard won information about the p53 protein, its mutations, structures, and activities learned in the basic science laboratory and translated to the clinic.

SUBMITTER: Levine AJ

PROVIDER: S-EPMC8852246 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Targeting the P53 Protein for Cancer Therapies: The Translational Impact of P53 Research.

Levine Arnold J AJ

Cancer research 20220201 3

It is only recently that drugs targeting K-RAS and Tp53 missense mutations have been developed, and along with the allele specific nature of some of these drugs comes the possibility of combining them with the immunologic therapies for cancers. It has taken about 40 years since their discoveries to understand the pathways they command, how they function, and how they interact with the environment of the cells they control. This communication focuses on the transfer of some of the hard won inform ...[more]

PMID: 35110395

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Project description:ObjectivesTo review the translational research (TR) performed in the Gynecologic Oncology Group (GOG) to evaluate ovarian cancer markers, profiles and novel therapies.MethodsProspective trials with stand alone or embedded TR objectives involving patient and specimen accrual as well as retrospective studies using banked specimens and resources were and continue to be performed in the GOG. Appropriate statistical methods are employed to evaluate associations with clinical characteristics and outcomes including tumor response, adverse events, progression free survival and overall survival.ResultsHighlights are presented for some of the collaborative and multidisciplinary TR conducted with the GOG to evaluate markers, pathway and novel therapeutics in epithelial ovarian, primary peritoneal and/or fallopian tube cancer. For example, in GOG 111, high immunohistochemical (IHC) expression of cyclin E was associated with a shorter median survival (29 versus 35 months) and an increased risk of death (hazard ratio [HR]=1.4, 95% confidence interval [CI]=1.0-2.1, p=0.05). In GOG 114/132, non-detectable immunoblot expression of maspin was associated with debulking status (p=0.034) and an increased risk of disease progression (HR=1.89, 95% CI=1.04-3.45, p=0.038) and death (HR=1.99, 95% CI=1.07-3.69, p=0.030) while high CD105-microvessel density (MVD), but not CD31-MVD in tumor was associated with increased risk of disease progression (HR=1.873, 95% CI=1.102-3.184, p=0.020) but not death. In GOG 172, low IHC expression of BRCA1 was associated with advanced stage (p<0.001), serous histology (p<0.001) and a reduced risk of disease progression (HR=0.64, 95% CI=0.42-0.96) and death (HR=0.51, 95% CI=0.32-0.83) while the CA/AA versus CC genotypes in C8092A in ERCC1 were associated with an increased risk of disease progression (HR=1.44, 95% CI=1.06-1.94, p=0.018) and death (HR=1.50, 95% CI=1.07-2.09, p=0.018).ConclusionsThe GOG has an extensive TR program that provides clues regarding the molecular and biochemical mechanisms of disease, treatments and outcomes in women with or at risk for a gynecologic malignancy.

Dataset Information

Targeting the P53 Protein for Cancer Therapies: The Translational Impact of P53 Research.

Publications

Targeting the P53 Protein for Cancer Therapies: The Translational Impact of P53 Research.

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