Thalidomide Derivatives Show Promise in Targeting Cancer-Causing Protein BCL-2

Researchers at Goethe University Frankfurt discovered thalidomide derivatives that can target and degrade the cancer-causing protein BCL-2, potentially leading to new cancer treatments. The derivatives were effective against mutated forms of BCL-2, which are often resistant to current treatments.

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Bijay Laxmi
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Thalidomide Derivatives Show Promise in Targeting Cancer-Causing Protein BCL-2

Thalidomide Derivatives Show Promise in Targeting Cancer-Causing Protein BCL-2

Researchers at Goethe University Frankfurt have discovered that derivatives of the drug thalidomide can target and degrade the cancer-causing protein BCL-2, potentially opening up new avenues for cancer treatment. The groundbreaking study, published in Cell Reports Physical Science, demonstrates the therapeutic potential of these modified thalidomide molecules.

Why this matters: This breakthrough could lead to more effective treatments for various types of cancer, potentially saving countless lives and improving the quality of life for cancer patients. Furthermore, the discovery of thalidomide derivatives' ability to target mutated forms of BCL-2 could pave the way for personalized cancer therapies.

Thalidomide has a complex history, initially marketed as a sedative in the 1950s before being found to cause severe birth defects when taken by pregnant women. However, in recent decades, researchers have uncovered its ability to inhibit blood vessel growth and treat certain cancers like multiple myeloma.

The Frankfurt researchers, led by Dr. Xinlai Cheng, created and tested various thalidomide derivatives for their ability to target proteins. They discovered three derivatives - C5, C6, and C7 - that can mark the BCL-2 protein for degradation. BCL-2 is crucial for cancer cell survival as it prevents programmed cell death. "We know that thalidomide is a molecular glue that can bind two proteins together, marking one of them for degradation," explained Dr. Cheng. "Our derivatives can target the BCL-2 protein, which is essential for the survival of cancer cells. This could be a new approach to cancer treatment."

The findings are particularly significant because cancer cells often have mutated forms of BCL-2 that are resistant to current treatments. The thalidomide derivatives were able to target and degrade these mutated versions. When tested in fruit flies with tumor cells, the treated flies showed significantly improved survival rates.

The study was a collaborative effort, with support from the German Research Foundation, the Frankfurt Cancer Institute, and the PROXIDRUGS project. Computer simulations performed with the Max Planck Institute for Biophysics helped model the interactions between the thalidomide derivatives and BCL-2.

While the results are promising, Dr. Cheng cautioned that the research is still in its early stages. Further studies will be needed to determine if these thalidomide derivatives can be effectively translated into clinical cancer treatments. However, the discovery of their ability to target and degrade the cancer-causing BCL-2 protein represents an exciting step forward in the ongoing battle against cancer.

Key Takeaways

  • Thalidomide derivatives can target and degrade cancer-causing protein BCL-2.
  • This breakthrough could lead to more effective treatments for various cancers.
  • Derivatives can target mutated forms of BCL-2, paving way for personalized therapies.
  • Treated fruit flies with tumor cells showed significantly improved survival rates.
  • Further studies needed to translate findings into clinical cancer treatments.