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Published on: July 25, 2020
Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors
Kiyoko Umene1, Kouji Banno1, Iori Kisu1
1Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Abstract:
Chemotherapy and surgery are important treatment strategies for gynecologic malignant tumors such as ovarian, cervical and endometrial cancer. However, many anticancer drugs currently available are cytotoxic and cause strong adverse reactions in patients. Aurora kinases have attracted increasing attention in recent years as serine/threonine kinases with various roles in cell division, including chromosomal agglutination and segregation, functions of centromeres, centrosomal maturation, spindle formation and cytokinesis. Aurora kinases are overexpressed in a number of cancers and recent studies have shown that they are involved in onco genesis and cause an aberrant increase in centrosome number, emergence of polykaryocytes and failure of cancer inhibition mechanisms. Thus, drugs that inhibit Aurora kinases are likely to exert anticancer effects in various fields, including the gynecologic field. Aurora kinase inhibitors exert antitumor effects in monotherapy and synergistic effects in combination therapy with taxane-based anticancer agents for gynecologic tumors and are likely to increase the efficacy of existing anticancer drugs. Current Aurora kinase inhibitors include ZM447439, Hesperadin, VX-680/MK-0457, AT9283 and Barasertib, and clinical trials are ongoing to verify the effects of these inhibitors.
Insights
Aurora kinase inhibitors show promise for treating gynecologic cancers by targeting cell division processes. These inhibitors may enhance existing chemotherapy effectiveness and reduce adverse reactions in patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Gynecologic cancers like ovarian, cervical, and endometrial cancer are often treated with chemotherapy and surgery.
- Current chemotherapies can cause significant adverse reactions.
- Aurora kinases, crucial for cell division, are overexpressed in many cancers, contributing to tumor growth.
Approach:
- Investigating Aurora kinase inhibitors as a targeted therapy for gynecologic malignancies.
- Evaluating the potential of these inhibitors in monotherapy and combination therapy.
- Reviewing current Aurora kinase inhibitors and ongoing clinical trials.
Key Points:
- Aurora kinases play vital roles in cell division, including chromosome segregation and spindle formation.
- Overexpression of Aurora kinases is linked to cancer development and progression.
- Inhibiting Aurora kinases may offer a novel therapeutic strategy for gynecologic cancers.
Conclusions:
- Aurora kinase inhibitors demonstrate antitumor effects in preclinical models of gynecologic tumors.
- These inhibitors show potential for synergistic effects when combined with existing treatments like taxanes.
- Further clinical investigation is warranted to establish the efficacy and safety of Aurora kinase inhibitors in gynecologic cancer patients.
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