Small cell lung cancer discovery could lead to new treatment

Small cell lung cancer discovery could lead to new treatment
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Scientists have discovered a way to halt the development of small cell lung cancer, and this could lead to new treatment options.

Small cell lung cancer is responsible for approximately 13% of lung cancer diagnoses. Patients typically have better outcomes when it is caught early before it has spread to the outside of the lung. However, it remains fast-growing and is often discovered after it has spread.

Scientists from UVA Cancer Center were seeking to understand the role of a mutation in the EP300 gene in the formation of small cell lung cancer tumours. Their experiment revealed that the gene creates a protein with surprising properties that foster or prevent the development of this cancer.

The protein has an essential role in tumour formation, making it an attractive target for researchers seeking to develop new treatments for small cell lung cancer (SCLC).

The research was published in the scientific journal Science Advances, and the work was funded by National Institutes of Health, a UVA “Three Cavaliers” grant, and an Adenoid Cystic Carcinoma Research Foundation grant.

New potential for small cell lung cancer

Currently, small cell lung cancer can be treated through surgery, chemotherapy, radiation, and immunotherapy, yet treatment does not cure cancer for most patients. This illuminates the urgent need for better treatment options.

UVA researchers Kwon-Sik Park, PhD, and John H. Bushweller, PhD led the study, and their new findings point to a potential new approach. The team made their surprise discovery in the course of investigating the role of the EP300 gene in the development of small cell lung cancer using genetically engineered mouse models.

They discovered that the protein the gene makes could both promote and suppress tumour formation. One component of the protein appeared to encourage cancer development, whilst another appeared to hinder it.

The scientists further investigated the tumour-promoting component, called KIX, and found it was a driving factor for small cell lung cancer development— cancer could not exist without it. Researchers noted that targeting KIX could offer a way to treat this cancer in patients and the KIX was referred to as a ’unique vulnerability.’

Targeting the KIX domain

To explore this vulnerability, Park reached out to UVA’s John H. Bushweller and Tim Bender, who previously had considered targeting the KIX domain.

“Based on this data, we are quite excited to pursue the development of a drug targeting the KIX domain, as this will likely have multiple applications for cancer treatment, particularly for SCLC and leukaemia,” said Bushweller, of UVA’s Department of Molecular Physiology and Biological Physics.

The researchers were pleased that their collaboration has produced such a promising lead in the effort to develop better therapies for small cell lung cancer.

“This study was one of the best examples for the interdisciplinary collaborations happening at UVA, spearheaded by talented and hardworking postdocs Kee-Beom Kim and Asish Kabra,” Park concluded.


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