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Clinical Candidates Targeting the ATR-CHK1-WEE1 Axis in Cancer
Lukas Gorecki1, Martin Andrs1,2, Jan Korabecny1
1Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
Abstract:
Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.
Insights
Targeting intra-S and G2/M checkpoints with ATR and WEE1 inhibitors shows promise for cancer treatment. While CHK1 inhibitors are still developing, ATR and WEE1 inhibitors offer a positive outlook for improving patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Medicinal Chemistry
Background:
- Selective cancer cell killing is a key goal, requiring understanding molecular differences between cancer and healthy cells.
- Targeting cell-cycle control, particularly intra-S and G2/M checkpoints, is a strategy for cancer therapy due to common defects in cancer cells.
Purpose of the Study:
- To review clinical candidates targeting kinases in the intra-S and G2/M checkpoints: ATR, CHK1, and WEE1.
- To provide insights into the current status and future perspectives of these inhibitors in anticancer treatment.
Main Methods:
- Review of clinical candidates targeting ATR, CHK1, and WEE1 kinases.
- Analysis of their current clinical trial status and therapeutic potential.
Main Results:
- ATR and WEE1 inhibitors have shown promising accomplishments in phase II clinical trials.
- CHK1 inhibitors are still in early stages and not yet clinically established.
Conclusions:
- ATR and WEE1 inhibitors present a positive outlook for enhancing patient survival in cancer treatment.
- Further development of these targeted therapies holds significant potential for the future of oncology.
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