Broad-Bayer collaboration leads to drug candidate for a hard-to-treat type of lung cancer

Broad Communications Scientists in the Broad-Bayer oncology alliance have developed a drug candidate, sevabertinib, that could be a new lung cancer treatment.
Illustration Credit: Agnieszka Grosso

An alliance of scientists at the Broad Institute and Bayer Pharmaceuticals have developed a drug candidate, sevabertinib, that could be a new treatment for a group of lung cancer patients who have few options today.

In a new study published in Cancer Discovery, the team described their efforts to develop sevabertinib. They tested the compound in various lung cancer models and showed its potential to treat non-small cell lung cancers that harbor certain mutations in the ERBB2 gene, which encodes the HER2 protein. These mutations occur in 2 to 4 percent of patients with non-small cell lung cancer, or roughly 40,000 to 50,000 people diagnosed globally each year. These patients tend to be women, including those who are younger, have never smoked, and have a poor prognosis. 

The study also reported data from two participants in Bayer’s phase 1/2 clinical trial of the compound. Based on these findings and other data from this ongoing clinical trial, the drug candidate is currently under Priority Review at the FDA, an expedited review of therapies that treat serious conditions. If approved, it would be the first FDA-approved cancer drug based on Broad discoveries, and the first new medicine from the Broad-Bayer oncology research alliance. 

When healing turns harmful: adrenal support cells tied to cancer origin

Image Credit: Scientific Frontline / AI generated

A new study from Karolinska Institutet, shows that support cells in the adrenal gland can regenerate hormone-producing tissue after birth. The same cells may also act as a starting point for adrenal tumors, offering new insights into cancer development and potential treatment strategies.

“We found that these glial-like cells not only help maintain healthy tissue but, in some paragangliomas, also carry the same tumor-initiating genetic event,” explains Susanne Schlisio, group leader at the Department of Oncology-Pathology and last author of the study. 

“In tumors with germline VHL mutations, subsets of these support cells showed loss of chromosome 3p, the ‘second hit’ leading to VHL inactivation. This suggests they may be the origin of certain tumors,” says Dr. Michael Mints, docent at the same department and co-corresponding author of the study.

Scientists help discover new treatment for many cancers

UniSA/CCB Professor Greg Goodall, part of the team that made the landmark discovery.
Photo Credit: Courtesy of University of South Australia 

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers identified the specific molecular mechanism responsible for actively transporting circular RNAs (circRNAs) from the cell nucleus to the cytoplasm.
• Methodology: The study mapped the export pathway and revealed that circRNAs utilize a transport mechanism resembling that of proteins, distinct from the export routes used by other forms of RNA.
• Key Data: Circular RNA possesses a closed-loop genetic structure that renders it inherently more stable and durable in the body compared to linear mRNA, which degrades rapidly.
• Significance: Understanding this transport pathway overcomes a major limitation of current RNA technology, validating circRNA as a robust platform for more effective genetic medicines.
• Future Application: These findings enable the development of a next generation of RNA therapeutics and vaccines with increased potency and longevity for treating cancer and other diseases.
• Branch of Science: Molecular Biology, Oncology, and Pharmacology.
• Additional Detail: The discovery confirms that circRNAs are not cellular byproducts but are actively transported to the cytoplasm to perform critical biological functions.