New research outlines an enhanced approach that could lead to treatments for prostate cancer and other diseases.
Researchers at UBC and BC Cancer have developed a new way to target proteins long considered “undruggable,” opening the door to new treatments for prostate cancer and other serious diseases.
Known as intrinsically disordered proteins, these molecular shapeshifters are extremely difficult to target with medication due to their flexible and ever-changing structure. They play a central role in a wide range of diseases—including cancer, neurodegenerative disorders, heart disease and autoimmune conditions.
In a study published today in Nature Signal Transduction and Targeted Therapy, the researchers demonstrate a new approach for designing drugs that bind more strongly to these proteins and block their disease-causing activity. In some cases, the compounds they developed bound up to a million times more tightly than any previously reported.
“This study shows that proteins previously thought to be undruggable can be drugged with remarkable efficacy,” said principal investigator Dr. Marianne D. Sadar, professor of pathology and laboratory medicine at the UBC faculty of medicine and distinguished scientist at BC Cancer. “The findings could have profound implications for the treatment of cancer and other diseases, providing a roadmap for the development of new treatments.”
Unlike most proteins, which fold into stable three-dimensional shapes, disordered proteins contain flexible regions that change as they interact with molecules inside cells. Because they lack fixed binding sites, they are extremely difficult to target with traditional drugs.
The new study focused on a specific protein, the androgen receptor, which fuels the growth of most prostate cancers.
Rather than fitting into a single fixed spot, the researchers developed compounds that interact with the moving region of the protein, freeze it in an inactive state, and prevent it from turning on genes that drive cancer growth.
“What surprised us was how effectively these molecules could attach to a protein that doesn’t have a fixed structure,” said Dr. Raymond Andersen, professor in UBC’s departments of chemistry, and earth ocean and atmospheric Sciences. “We were able to shut down the androgen receptor even in situations where current prostate cancer drugs stop working.”
Story from UBC Science. Read the full story here.