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New cancer therapy: Researchers reveal secret of the PLK1 protein!
Research at Saarland University reveals new approaches against cancer by inhibiting the protein PLK1 and its interaction with IGF2BP2.
New cancer therapy: Researchers reveal secret of the PLK1 protein!
A research team from Saarland University and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) is studying the protein Polo-like Kinase 1 (PLK1), which plays a crucial role in cell division. This protein promotes the growth and mutation of tumor cells, making it an interesting target for new cancer therapies. Despite the promising approaches, direct inhibition of PLK1 has so far shown only limited clinical benefits for patients. The detailed results of these studies were published in the journal Cell Genomics, which underlines the relevance of the work.
The researchers have identified IGF2BP2 as an alternative target to influence PLK1 in tumors. It turns out that IGF2BP2 and PLK1 interact closely with each other. Inhibiting IGF2BP2 leads to a significant reduction in PLK1 and thus also in tumor growth. Without IGF2BP2, the energy metabolism of cancer cells is disrupted, which is particularly visible in the mitochondria. This fact could open up new avenues for the development of more effective cancer therapies.
Scientific background to PLK1
PLK1 belongs to the Polo-like kinase family and is crucial for various mitotic processes. It is a conserved enzyme found from yeast to humans. PLK1 is involved in several critical processes, including the G2/M transition, spindle assembly, and chromosome distribution. PMC reports that Deregulation of PLK1 can lead to a variety of problems, including mitotic errors and tumor-inducing genome instability.
PLK1 overexpression is observed in many cancers and often correlates with poor prognosis. The goal of therapeutically inhibiting PLK1 could therefore be crucial for new treatment approaches. Scientists are already using various methods to inhibit PLK1, including antisense oligonucleotides and small molecules. This is demonstrated by an analysis that examines the effectiveness and selective binding of PLK1 inhibitors.
Clinical developments and challenges
Currently, many PLK1 inhibitors, such as BI 2536 and BI 6727, show promising efficacy, but are accompanied by significant challenges in selectivity and toxicity. Clinical successes to date are limited, particularly in advanced stages of cancer. PMC notes that Combination therapies in which PLK1 and other target structures are addressed simultaneously promise enhanced treatment effects.
Several studies are investigating PLK1 inhibitors in combination with chemotherapy drugs as well as targeted therapies. For example, BI 2536 and eribulin were tested in the treatment of rhabdomyosarcomas. The combination of BI 6727 with cisplatin shows an improved response in cervical cancer. Future research should focus on also combining PLK1 inhibitors with immunotherapies and identifying new co-targets to further optimize therapeutic outcomes.
Overall, ongoing research on PLK1 and IGF2BP2 could be a crucial step in the development of new therapeutic strategies against aggressive tumors.