Improving the Odds by Understanding the Mechanism of Chemotherapy Resistance

By Clint Williams

What is true in gangster movies is true with cancer tumors. The bad guys have bodyguards, but instead of threatening death, they try to prevent it!

Research by Dr. Kelly Goldsmith, a pediatric cancer specialist at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta, is targeting the molecular bodyguards protecting particularly nasty cancer cells. CURE Childhood Cancer is proudly funding Dr. Goldsmith’s research.

Neuroblastoma is a cancer that develops in the nerve tissues of the adrenal gland, abdomen, chest and neck. Apart from brain tumors, it is the most common solid tumor among children and about half of neuroblastoma cases are found in children younger than two years old.

The gravity of a diagnosis of neuroblastoma varies according to the tumor’s classification among three risk categories: low, intermediate, and high. A low-risk tumor is highly curable, but high-risk neuroblastoma kills more than half of the children with the disease.

“The majority of those children die from recurrent disease because the cancer becomes resistant to chemotherapy,” says Goldsmith, also an Assistant Professor of Pediatrics at Emory University School of Medicine. “For this tumor, we’ve got to figure out a better way to make the children chemotherapy sensitive again or to therapeutically target the tumor without harming normal tissues.”

Apoptosis, or programmed cell death, is a method by which cells are eliminated from the body without releasing harmful substances to surrounding normal tissues. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells, like pre-cancerous ones.

Chemotherapy and radiation kill tumor cells by triggering apoptosis. Therefore, many aggressive tumors, including neuroblastoma, have found ways to survive chemotherapy by altering their apoptosis genes.

Neuroblastoma cells depend on certain members of the Bcl-2 family of proteins to protect them from apoptosis. Other members of the Bcl-2 family, called BH3-only proteins, can trigger apoptosis.  Research by Goldsmith using small chains of amino acids mimicking BH3 proteins (BH3 peptides) has potently killed neuroblastoma cells in test tubes and neuroblastoma tumors in mice.

She has also determined what Bcl-2 proteins a tumor depends on for survival by testing small tumor organelles such as mitochondria with the same BH3 peptides.

The goal is to develop profiles of tumor cells, breaking them down to the bare essentials, to best determine what drugs to use in treatment.

But establishing the effectiveness against cancer cells in test tubes and test sujects is just one step along the way to treating children. The next phase of research, Goldsmith says, requires fresh neuroblastoma tumor tissue.

But there are many competing demands for the limited supply of tumor tissue and Goldsmith will be learning and developing techniques to make the best use of the samples.

Goldsmith is building on research she did at Children’s Hospital of Philadelphia where she was recruited from in the fall of 2009.  Goldsmith is now in Atlanta to be closer to family – and – because this is where she can best help sick children by turning research results into practical treatment.

“One thing I really like about being here is the drive to translate from bench to bedside,” Goldsmith says. “I think that is such a huge focus and here they are really trying to make it a reality.”

“CURE is proud to be supporting Dr. Goldsmith’s promising research,” remarks Executive Director Kristin Connor.  “We are very concerned with making new treatments available to children as quickly as possible. We are so pleased that Dr. Goldsmith shares these urgent concerns as she works to find cures for a very devastating form of pediatric cancer.”

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1 Comment

Filed under Childhood Cancer, Research, Support CURE

One response to “Improving the Odds by Understanding the Mechanism of Chemotherapy Resistance

  1. Hi hunnie, sweet site! I genuinely like this article.. I was wondering about this for a while now. This cleared a lot up for me! Do you have a rss feed that I can add?

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