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Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies

Katsutoshi Oda1, Yuji Ikeda1, Tomoko Kashiyama1

  • 1Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

The Journal of Obstetrics and Gynaecology Research
|April 21, 2016
PubMed

Insights

Genomic analysis reveals key cancer pathways like TP53 and phosphatidylinositol 3-kinase. This review discusses targeted drugs, including dual PI3K/mTOR inhibitors, for gynecologic malignancies.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Genomic analysis has identified critical signaling pathways in human cancers.
  • Gynecologic malignancies have limited molecular-targeted drug options.
  • TP53 and phosphatidylinositol 3-kinase (PI3K) pathways are frequently mutated and are key cancer targets.

Purpose of the Study:

  • To review the functions of TP53 and PI3K signaling pathways in cancer.
  • To discuss molecular-targeted drugs currently in clinical trials for gynecologic malignancies.

Main Methods:

  • Literature review of genomic analysis and molecular-targeted therapies.
  • Focus on TP53 and PI3K signaling pathways.
  • Analysis of drugs targeting these pathways and related pathways.

Main Results:

  • Identified dual PI3K/mTOR inhibitors (NVP-BEZ235, DS-7423, SAR245409), an mTOR inhibitor (everolimus), an MEK inhibitor (pimasertib), an autophagy inhibitor (chloroquine), a CDK4/6 inhibitor (PD0332991), and a PARP inhibitor (olaparib).

Conclusions:

  • TP53 and PI3K pathways are crucial targets for cancer therapy.
  • Several molecular-targeted drugs are under clinical investigation for gynecologic cancers, offering potential new treatment avenues.
Keywords:
TP53endometrial cancermolecular target therapyovarian clear cell carcinomaphosphatidylinositol 3 kinase

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