A Good BET On Liposarcoma Treatment

Scientists in Singapore have found that BET proteins play a huge role in the development of liposarcoma, making them a target for future anticancer drugs.

AsianScientist (Jun. 25, 2019) – In a study published in Nature Communications, a research group in Singapore has identified a family of proteins that is associated with liposarcoma (LPS), a type of cancer that develops from fat cells.

Liposarcoma is currently treatable by surgery and radiation therapy. Chemotherapy using a recently approved chemotherapy agent, trabectedin, can also be prescribed to patients who are at high risk of recurrence or metastasis. The effectiveness of trabectedin, however, can be hampered by clinical toxicity and acquired resistance to the treatment.

In the present study, researchers led by Professor H. Phillip Koeffler at the Cancer Science Institute of Singapore, in collaboration with colleagues at the National University of Singapore, performed a detailed analysis of the genetic elements responsible for the development of LPS in samples from patients who have recurrent LPS, or whose cancers are resistant to standard therapies. They found that the bromodomain and extraterminal (BET) protein family is linked to LPS development and progression.

The researchers then investigated the inhibition of LPS development using a BET protein degrading agent, ARV-825. They demonstrated that ARV-825 disrupted the core transcriptional program in LPS and prevented the cancer from progressing. In addition, the researchers observed that LPS cells resistant to trabectedin were also susceptible to the depletion of BET proteins, thereby making BET protein a promising drug target.

“The findings of our study have important clinical implications for LPS. It uncovers the essential roles and desirable therapeutic potentials of BET proteins in LPS, which paves the way for new therapeutic strategies to be designed against the ailment,” said Koeffler. “The effectiveness of ARV-825 in suppressing LPS development described in our study also encourages further translation of BET protein degraders into effective anticancer drugs.”

Moving forward, the researchers will look into ways to reduce LPS patients’ resistance to drug treatments and identify other targets that may be hindering response to treatments.

The article can be found at: Chen et al. (2019) Bromodomain and Extraterminal Proteins Foster the Core Transcriptional Regulatory Programs and Confer Vulnerability in Liposarcoma.


Source: National University of Singapore; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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