HER2 inhibitors(Boehringer Ingelheim)

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. “This is an extraordinary time for the development of new treatments for patients with cancer and so many other diseases,” said study co-leader Matthew Meyerson , an institute member at the Broad, the Charles A. Dana Chair in Human Cancer Genetics at Dana-Farber Cancer Institute, and professor of genetics and medicine at Dana-Farber and Harvard Medical School. “Our work on sevabertinib is a real proof-of-concept that we can use genetic insights from cancer patients to develop next-generation cancer therapeutics. I’m hopeful that future collaborations between the Broad and industry partners like Bayer will continue to yield discoveries that could one day improve patient health.” The work was also led by co-senior author Heidi Greulich , an institute scientist and senior group leader in the Cancer Program at the Broad, along with first author Franziska Siegel, research portfolio lead for oncology research at Bayer Pharmaceuticals. In 2013, the Broad and Bayer launched a research alliance to find cancer drug targets and novel therapeutic approaches. One of the alliance’s first efforts was to search for potential drugs that target a specific mutation in lung cancer patients that Greulich, Meyerson, and Broad colleagues had studied nearly a decade earlier. In 2005, the Broad team reported that some patients who didn’t respond to lung cancer drugs that targeted a protein called EGFR had a mutation in their tumors known as an “exon 20 insertion” — an extra bit of DNA tucked in at a specific location in the EGFR gene. They suggested that new drugs targeting this mutation could potentially benefit these patients. In the new paper, the team showed that sevabertinib could target exon 20 insertions in both EGFR and in a related protein, HER2. The drug candidate inhibits an enzyme in the cell, called a “tyrosine kinase”, that helps promote cancer cell growth and survival, so the scientists theorized that blocking the enzyme could slow growth in tumors or shrink them. Using cell models developed at Broad to carry the HER2 exon 20 insertions, the researchers demonstrated that the compound slowed the growth of cells by targeting the mutated HER2 protein, while largely not interfering with normal EGFR. Other results from experiments in cells suggest that the drug candidate might work in cases where other HER2 inhibitors might not, and may have activity in other cancers, such as breast and gastroesophageal that are marked by high HER2 levels. In animal models carrying tumors with the HER2 mutations, the drug candidate shrank the tumors. And in two clinical trial participants who had already tried standard-of-care treatments, sevabertinib shrank lung tumors with the HER2 exon 20 insertion mutation. “The development of this new drug candidate speaks to the power of collaboration, where we each bring different knowledge and skills,” said Greulich. “We faced challenges in this project, but through persistence and long-term combined efforts, we were able to find a potential new solution for a group of patients who need more options.” Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.