Resisting Cancer's Resistance

Neuroblastoma responds to combination of medications

(RxWiki News) One of the many cruelties of cancer is that it may temporarily shrink in the presence of new drugs, only to come roaring back later.

A new dual approach may help children with neuroblastoma, a rare but deadly form of brain cancer.

Adding a second class of drugs called mTOR inhibitors boosts the effectiveness of a targeted therapy - Xalkori (crizotinib) - in children with neuroblastoma.

"Talk to your oncologist about combination therapies."

Researchers at The Institute of Cancer Research in London, the Dana-Farber Cancer Institute and Children's Hospital in Boston discovered the effectiveness of this combination therapy.

Xalkori is approved by the US Food and Drug Administration (FDA) for late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) that express the abnormal anaplastic lymphoma kinase (ALK) gene.

During a recent trial, the medication showed positive results in treating children with cancer.

Study investigators learned that neuroblastoma, which is a cancer of the developing nervous system, is driven by a cancer-promoting gene known as ALK.

Crizotinib targets the ALK gene. While the drug offers initial success, it can eventually stop working after the cancer becomes resistant to it.

Senior author Dr. Louis Chesler, leader of the neuroblastoma drug development team at the Institute of Cancer Research, said, "We have identified a very promising way to overcome crizotinib resistance in neuroblastoma, by adding a second drug called an mTOR inhibitor. Many mTOR inhibitors are already in adult clinical trials."

Children with neuroblastoma often have defects in the MYCN gene. Mutations in this gene, which is difficult to target, are associated with a more aggressive form of the brain cancer.

The scientists found that the two altered genes (ALK and MYCN) turn on a pathway (PI3K/AKT/mTOR) that's thought to be involved in numerous adult cancers.

When the mTOR inhibitor was combined with Xalkori, the devious work of the two genes was blocked, thus overcoming tumor resistance.

Dr. Chesler said, "Our study may also have relevance for adult patients with ALK-driven lung cancer and lymphoma who develop resistance to crizotinib..."

This study was published July 11 in the journal Cancer Cell.

The research was supported with funds from various sources, including the Neuroblastoma Society, Cancer Research UK, Sparks, the children's medical research charity and The Rooney Foundation.

Review Date: 
July 16, 2012