National Cancer Research Month: What’s happening at Sanford-Burnham

By Bruce Lieberman
May 18, 2013
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May is National Cancer Research Month, so we thought we’d highlight exciting cancer research underway at Sanford-Burnham. Today, we focus on a few of the strategies our researchers are pursuing to better understand the pathologies of cancer tumors—and stop them in their tracks.

Targeting childhood brain cancer

Robert Wechsler-Reya, Ph.D., and his colleagues study the relationship between normal human development and cancer. They’re interested in how normal stem cells decide when to divide, when to specialize into other types of cells, and what tissues to become. When those processes break down, cancer can develop.

Dr. Wechsler-Reya’s group was the first to identify a new type of stem cell that develops into many different cell types in the cerebellum. But if this stem cell acquires certain mutations, it can result in medulloblastoma, the most common malignant brain cancer in children. Medulloblastomas are often treatable through surgery, radiation, and chemotherapy, but these treatments can dramatically reduce cognitive function and a child’s overall quality of life.

Dr. Wechsler-Reya’s team is identifying drug candidates that more specifically target tumors seen in medulloblastoma, to avoid the dangerous side effects of radiation and chemotherapy. Over the next few years, they hope to use this information to develop more effective therapies.

Converting cancer stem cells into normal cells

What if the best way to stop a tumor is not to kill it, but to turn it into something else? That’s the idea behind “differentiation therapy,” a new approach that prompts cancer stem cells to change into healthy, functioning cells—stopping tumors at their earliest stages.

In a recent study by Sanford-Burnham’s Robert Oshima, Ph.D., Masanobu Komatsu, Ph.D., and others, a mouse model of aggressive breast cancer was treated with bosutinib (SKI-606), a drug currently under development to treat advanced malignant tumors. The potential drug prevented the appearance of tumors in more than half of the treated mice, and it reduced tumor growth in older animals with pre-existing tumors.

Bosutinib was successful not because it killed cancer cells, but because it induced them to change into normal functioning cells. Unlike chemotherapy and radiation, which kill every cell they encounter, differentiation therapy disarms cancer cells without the dangerous side effects. Dr. Oshima’s team is now searching for other drug candidates that might induce cancer stem cell differentiation.

Carbohydrates that are good for you

One of the ways that tumors develop is when carbohydrates on a cell’s surface, which influence many cellular functions, become misplaced or malfunction.

Minoru Fukuda, Ph.D., and his team found that one type of carbohydrate, called “core 3 O-glycans,” suppresses tumor formation and metastasis—and it’s this same carbodydrate that’s seen at abnormally low levels in cancer cells.

Dr. Fukuda’s lab found that when core 3 O-glycans were artificially expressed on human prostate cancer cells, those cells produced much smaller tumors and almost no metastases. Parent cancer cells that do not express core 3 O-glycans, in contrast, produce robust tumors. Dr. Fukuda’s team also learned that the expression of core 3 O-glycans decreases the formation of integrin complexes, which play a role in a cell’s ability to migrate—a defining feature of cancer metastasis.

This means that certain carbohydrates on normal cells, such as core 3 O-glycans, and the enzymes that synthesize them, can act as tumor suppressors. Drug therapies that boost the activity of those enzymes may prove effective in treating cancer tumors.

Visit us again next week to learn about our research into how cell signaling is leading to new cancer treatment approaches. 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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