Stanford, SRI to support development of novel drugs to treat triple-negative breast cancer

Close to 20 percent of breast cancers are triple-negative, a type of tumor that lacks the three most common receptors that fuel most breast cancer growth. These tumors are unresponsive to hormone therapy or drugs targeting these receptors.

The research collaboration will explore the use of a preclinical drug known as sudemycin D6 that targets a "molecular machine" called the spliceosome. The spliceosome is critical to the basic biological transformation of DNA to RNA to proteins.

It "edits" raw RNA transcribed from DNA, cutting and piecing together stretches of code to form the instructions for creating various functional proteins, much as a film editor crafts a finished movie from raw footage. If this biological editor complex is defective, proteins that ultimately result from its actions can be dysfunctional and lead to various forms of cancer, including triple-negative breast cancer.

The research team will be led by Thomas R. Webb, Ph.D., director of Medicinal Chemistry at SRI Biosciences, a division of SRI International, and George Sledge, M.D., professor and chief of the Division of Oncology at Stanford University Medical Center.

"As both a medicinal chemist and cancer survivor, I know that new treatments are desperately needed for cancer," said Webb.

"It is my greatest hope that we can combine the unique strengths of SRI Biosciences and the Stanford Cancer Institute to make long-lasting impact in the treatment of triple-negative breast cancer, where unfortunately there are currently few effective therapeutic options. The strategy may also work for a range of other cancers, including lymphoma, melanoma, and certain brain and colon cancers."

"Stanford and SRI both have unique strengths, and together we can create something wonderful for patients with cancer: new treatments that are more effective and less toxic," said Dr. Sledge.

Webb’s research group designed sudemycin D6 to neutralize the SF3B1 protein of the spliceosome with enhanced activity and duration of action as well as less toxicity than previous spliceosome targeting agents. The team has also developed a marker tumor cell line that fluorescently glows when treated with sudemycin D6. This advance enables real-time monitoring of the drug’s activity, which will support translation to the clinical setting.

The SRI Biosciences and Stanford Cancer Institute collaboration is the first step in determining whether sudemycin D6 may be effective against triple-negative breast cancer. As part of the research, tumor samples from anonymous patients will be analyzed at the molecular level and examined in mouse models.

Nathan Collins Ph.D., vice president of Pharmaceutical and Chemical Technologies in SRI Biosciences and Sanjay Malhotra Ph.D., FRSC, associate professor of radiation oncology at Stanford are co-directors of the SRI Biosciences – Stanford Drug Discovery and Development Program that was announced in January 2016 to combine the translational capabilities of both organizations focused on creating a pipeline of innovative cancer drugs for unmet needs in oncology.

According to Malhotra, "The Webb-Sledge collaboration is an excellent example of how translation of a lab discovery into clinic can be expedited though the Stanford-SRI Drug Discovery and Development program. This is a new program, and we hope our wider research community will benefit from our joint efforts."

"Building on our collaborative program we are delighted to be working with the Stanford Cancer Institute to develop therapies for serious unmet needs in the treatment of cancer," added Collins.