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Mps1/TTK: a novel target and biomarker for cancer
Yuan Xie1, Anqiang Wang1, Jianzhen Lin1
1a Department of Liver Surgery , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Abstract:
Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits. Mps1 can be utilized as a new immunogenic epitope, which is able to induce potent cytotoxic T lymphocyte activity against cancer cells while sparing normal cells. Some clinical trials have validated its safety, immunogenicity and clinical response. Thus, Mps1 may be a novel target for cancer therapy. Mps1 is differentially expressed between normal and malignant tissues, indicating its potential as a molecular biomarker for diagnosis. Meanwhile, the discovery that it clearly correlates with recurrence and survival time suggests it may serve as an independent prognostic biomarker as well.
Insights
Monopolar spindle 1 (Mps1) is crucial for cell division and highly expressed in cancers. Targeting Mps1 offers a promising strategy for cancer therapy and diagnosis due to its immunogenicity and biomarker potential.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint, ensuring accurate chromosome distribution.
- Mps1 expression is typically low in normal tissues but elevated in various human malignancies.
Purpose of the Study:
- To evaluate Mps1 as a potential therapeutic target and diagnostic/prognostic biomarker in cancer.
- To explore the immunogenic properties of Mps1 for cancer immunotherapy.
Main Methods:
- Analysis of Mps1 expression in normal versus malignant tissues.
- Investigation of Mps1 inhibitors' efficacy on cancer cell proliferation.
- Assessment of Mps1 as an immunogenic epitope inducing cytotoxic T lymphocyte activity.
- Review of clinical trial data on Mps1-targeted therapies.
Main Results:
- Mps1 inhibitors demonstrate anti-proliferative effects and survival benefits in preclinical cancer models.
- Mps1 serves as an immunogenic epitope, eliciting potent anti-cancer T cell responses.
- Clinical trials confirm the safety, immunogenicity, and clinical response of Mps1-based strategies.
- Differential expression of Mps1 correlates with cancer recurrence and survival.
Conclusions:
- Mps1 represents a novel and promising therapeutic target for various cancers.
- Mps1's distinct expression patterns and immunogenicity support its use as a diagnostic and prognostic biomarker.
- Targeting Mps1 offers a dual approach for cancer treatment: direct inhibition and immunotherapy.
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