This new research collaboration will look into the potential of a preclinical drug known as sudemycin D6 that targets the spliceosome – a kind of a “molecular machine” pivotal to the basic biological transformation of DNA into RNA and proteins. In a way, the spliceosome edits raw RNA transcribed from DNA by separating and reassembling stretches of code to form the instructions necessary to create several functional proteins – like a film director would craft a finished movie from the unedited footage. If this biological complex edition process is defective, the proteins that will ultimately result from its action will be dysfunctional, potentially leading to multiple forms of cancer, including TNBC.
Nearly 20 percent of all breast cancers are triple-negative, which means they do not have the three most common receptors that fuel most breast cancer growth. These types of tumors are also unresponsive to hormone therapy or targeted-drugs.
Thomas R. Webb, Ph.D., who serves as the director of Medical Chemistry at SRI Biosciences, will lead the research team, together with George Sledge, M.D., who is professor and chief of the division of Oncology at Stanford University Medical Center:
“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,” Sledge said in a press release.
“As both a medicinal chemist and cancer survivor, I know that new treatments are desperately needed for cancer,” Webb said. “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.”
The collaboration between SRI Biosciences and Stanford Cancer Institute will be the first step toward understanding whether sudemycin D6 can be an effective treatment against TNBC. Webb’s research group will collect tumor samples from anonymous patients and analyze them at a molecular level in animal models.
The research team designed sudemycin D6 to neutralize the SF3B1 protein of the spliceosome with enhanced activity and action duration and holding less toxicity than previous agents targeting the spliceosome. Additionally, Webb’s group developed a marker tumor cell line that has a fluorescent glow when it receives sudomycin D6 treatment. The latter allows researchers to monitor the drug’s activity in real-time, supporting translation in a clinical context.
The Stanford Drug Discovery and Development Program was launched in January to combine the translational capabilities of the two parties to hopefully create a pipeline of novel cancer drugs for unmet oncological needs.
“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,” said SRI Biosciences’ Co-Director Sanjay Malhotra, Ph.D., FRSC, who is also an associate professor of radiation oncology at Stanford.