Grand Rapids, Mich. (Nov. 15, 2013) – A discovery by scientists at Van Andel Institute offers promise of an innovative treatment strategy to impair the growth of cancer cells. The study identifies two compounds that slowed tumor growth while protecting normal tissue. The results may lead to an improved and safer therapy for a variety of human cancers.
The new report, “Small molecule intramimics of formin auto-inhibition: a new strategy to target the cytoskeletal remodeling machinery in cancer cells,” was carried out at the Van Andel Research Institute in collaboration with scientists from Grand Valley State University and Kalamazoo Valley Community College’s Michigan High Throughput Screening Center and published this week in the journal Cancer Research.
“This discovery could lead to novel cancer therapies for hard to treat cancers and potentially serve as an alternative or an adjuvant to Taxol or Vinblastine, agents commonly used in chemotherapy to treat breast, ovarian, lung, testicular and certain blood cancers,” said Dr. Arthur S. Alberts, Ph.D., Professor and head of the Laboratory of Cell Structure and Signal Integration at Van Andel Institute and the senior author of the study.
All cells have an internal structural framework that makes it possible for the cell to move and divide. This “cytoskeleton” is a valid target for currently used chemotherapeutic drugs like Taxol and Vinblastine. These drugs successfully target the building blocks of the cytoskeleton to keep cancerous cells from growing and dividing, which can prevent tumor growth.
The study describes a new class of compounds called Intramimics that target a family of proteins in the cell called formins. “Formins are the masons of the cell that assemble the individual building blocks into the structures that comprise the cytoskeleton,” explained Dr. Alberts, who has spent the past fifteen years studying the genetics, molecular and cell biology of formins in cancer and other diseases.
Because their mechanism of action is distinct from currently available chemotherapeutic agents, it is hoped that the Intramimic compounds can specifically target cancer cells and spare healthy cells without the dose-limiting side effects experienced with Taxol and Vinblastine.
The two Intramimic compounds identified in this study were shown to trigger stabilization of microfilaments and microtubules that make up the cellular cytoskeleton. Experiments on cancer cells showed that Intramimics affected changes in gene expression that are associated with impaired cell growth and programmed cell death (apoptosis), that would be expected to reduce tumor size or slow tumor growth. Indeed, in another experimental system, the Intramimics did slow tumor growth. Taken together these studies suggest this strategy will be effective for treating solid tumors. Other preliminary evidence suggests potential application in the treatment of blood cancers as well.
“This discovery provides a new development regarding clinically validated drug targets in an area of research where few new strategies have emerged,” Dr. Alberts said. “Intramimics will serve as leads for further exploration and pharmacological development.”
The complete paper can be found on the Cancer Research website.
About Van Andel Institute
Established by Jay and Betty Van Andel in 1996, Van Andel Institute (VAI) is an independent research and educational organization based in Grand Rapids, Mich., dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. Van Andel Research Institute (VARI), VAI’s research arm, is dedicated to studying the genetic, cellular and molecular origins of cancer, Parkinson’s and other diseases and working to translate those findings into effective therapies. This is accomplished through the work of more than 200 researchers in on-site laboratories and in collaborative partnerships that span the globe. Find out more about Van Andel Institute or donate by visiting www.vai.org