National Cancer Research Month: Our signal transduction research

By Bruce Lieberman
May 23, 2013
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As you probably know by now – May is National Cancer Research Month, and this is the second post in our blog series to profile cancer research programs underway at Sanford-Burnham. This week, we review a few of the programs that focus on a malfunctioning signaling process in cells called “signal transduction.” Signal transduction occurs when a molecule outside of a cell activates a receptor on the cell, triggering a response inside. This vital process drives a variety of functions, including how a cell senses and responds to environmental change and communicates with other cells. When signal transduction pathways malfunction, a variety of diseases can arise, including cancer.

Getting to the molecular heart of melanoma

Over the past two decades, Ze’ev Ronai, Ph.D., and his laboratory team have studied protein kinases such as JNK, AKT,  and PDK1. These enzymes are important components of signaling pathways in cells that are commonly down-regulated in melanoma, a type of skin cancer. As a result, the enzymes serve as potential drug targets so they can become active again.

Dr. Ronai’s team also studies a protein called activating transcription factor 2 (ATF2), which is associated with a poor prognosis in melanoma. This protein regulates a vast array of genes important for the healthy functioning of cells. The Ronai team identified a protein kinase named PKCɛ as the component that makes ATF2 cancer-causing in melanoma. In normal tissues, PKCɛ  is not as active, which allows ATF2 to protect the body against the formation of tumors.

Using this information, Dr. Ronai’s team, in collaboration with Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics, is searching for small molecules that would confer the anti-cancer function of ATF2, thereby resuming ATF2’s ability to prevent the development of tumors. This approach could offer new therapeutic options for melanoma, and possibly other tumors where PKCɛ  promotes ATF2’s cancer-causing malfunction.

Targeting drugs for chemotherapy and tumor imaging

For many years, Elena Pasquale, Ph.D., has studied the relationship between a cell-surface receptor called Eph and proteins called ephrin. Eph receptors are like antennae that protrude from the surface of a cell. They foster cell-to-cell communication by binding to ephrin proteins on the surfaces of neighboring cells. Eph receptors, researchers have learned, appear more often in cancer cells than they do in normal ones.

Dr. Pasquale is now creating peptides that attach selectively to Eph receptors. Her collaborator, Maurizio Pellecchia, Ph.D., has developed a way to combine one of these peptides with a chemotherapy drug. The resulting combination amounts to a guided missile with a potent anti-cancer payload. Such specially designed drugs could be made to target cancer tumors, making them more effective while greatly reducing side effects.

In other work, Sanford-Burnham researchers have attached special chemicals to another Eph-targeting peptide that Dr. Pasquale developed to image tumors in mice. This approach might enable physicians to use MRI or PET scans to detect tumors early.

Visit us again next week for the last post in our National Cancer Research Month blog series about therapies to watch. Also go to Facebook.com/CancerResearchMonth to learn more about National Cancer Research Month and follow the conversation on Twitter, #NCRM13.

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