دورية أكاديمية
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Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.

التفاصيل البيبلوغرافية
العنوان: Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.
المؤلفون: Ibanez KR; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Huang TT; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Lee JM; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
المصدر: Cells [Cells] 2024 Jun 19; Vol. 13 (12). Date of Electronic Publication: 2024 Jun 19.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Genital Neoplasms, Female*/drug therapy , Genital Neoplasms, Female*/genetics , Genital Neoplasms, Female*/pathology , Drug Resistance, Neoplasm*/drug effects , Phosphoinositide-3 Kinase Inhibitors*/pharmacology , Phosphoinositide-3 Kinase Inhibitors*/therapeutic use , Signal Transduction*/drug effects, Humans ; Female ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Animals
مستخلص: The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or in combination for solid tumors such as renal cell carcinoma or breast cancer. However, despite the high prevalence of PI3K pathway alterations in gynecological cancers and promising preclinical activity in endometrial and ovarian cancer models, PI3K pathway inhibitors showed limited clinical activity in gynecological cancers. In this review, we provide an overview on resistance mechanisms against PI3K pathway inhibitors that limit their use in gynecological malignancies, including genetic alterations that reactivate the PI3K pathway such as PIK3CA mutations and PTEN loss, compensatory signaling pathway activation, and feedback loops causing the reactivation of the PI3K signaling pathway. We also discuss the successes and limitations of recent clinical trials aiming to address such resistance mechanisms through combination therapies.
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معلومات مُعتمدة: ZIA BC011525 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: PI3K/AKT/mTOR inhibitors; combination treatment; gynecological cancer; resistance mechanisms; targeted therapy
المشرفين على المادة: 0 (Phosphoinositide-3 Kinase Inhibitors)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
0 (Protein Kinase Inhibitors)
تواريخ الأحداث: Date Created: 20240626 Date Completed: 20240626 Latest Revision: 20240628
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC11201409
DOI: 10.3390/cells13121064
PMID: 38920692
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells13121064