Resisting Cancer's Resistance | dailyRx

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 Hopsital in Boston discovered the effectiveness of this combination therapy.

Xalkori is approved by the U.S. 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.

Brain Tumors

Each year in the United States, over 25,000 people will be newly diagnosed with some form of primary malignant brain tumor, and over 90,000 people are currently living with the disease and undergoing treatment. Approximately 13,000 of these patients will die from the disease, representing 2% of all cancer deaths.

Brain tumors encompass a wide variety of types of cancer, some more aggressive than others. They include:

• Glioblastoma multiforme (GBM) ? A deadly tumor forming in the white matter of the brain. Makes up 52% of all cerebral tumors and most common in white and Asian men over age 50. It is very difficult to treat and average survival after diagnosis is 14 months.
• Astrocytoma ? a tumor that forms from the glial cells in the brain (support cells for neurons). These can be benign or malignant (GBM is a form of astrocytoma) and appear in young children as well.
• Oligodendroglioma ? arise from the oligodendrocytes (insulating cells for axoms). They appear mostly in adults around age 35 and represent about 10% of all primary brain tumors and tend to recur after treatment.
• Ependymoma ? arises from tissues in the brain that surround the drainage system of the brain. They represent about 5% of adult brain tumors, and 10% of pediatric brain tumors, peaking at age 35 and earlier at age 5. Often they end up causing hydrocephalus, or ?water on the brain."

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Brain tumors are caused by a change in genetics, much like any other cancer that causes cells to grow out of control. Some brain tumors are associated with specific chromosomal changes, but in most cases, the cause of a brain tumor is unknown, and due to some combination of genetic instability and environmental damage.

Symptoms of a brain tumor depend mainly on the size of the tumor and where it is located in the brain. Because the brain is housed in the skull, a growing tumor will cause something called mass effect, where the enlarging tumor is taking up too much space and cause increased pressure in the brain. This can cause terrible headaches, nausea, vomiting, and changes in consciousness among other specific signs. In other cases, the growing tumor may encroach upon a part of the brain that has a specific function, and cause that function to cease. Depending on what part of the brain the tumor is in, language, motor coordination, vision, balance, and paralysis can occur. In both cases, a brain tumor can present immediately or after several years of growing.

Diagnosis of a brain tumor will ultimately be made by CT scan and MRI. Treatment of brain tumors may involve surgery, radiation, and chemotherapy. Additionally, MRI-guided laser ablation is frequently used, a technique that involves placing a laser directly into the tumor, and then guiding the laser to destroy the tumor with heat while leaving the surrounding brain tissue undisturbed. Each modality presents its own risks and benefits. Surgery is sometimes not possible because of risk to damage of vital brain structures necessary for life.

Prognosis for a brain tumor is entirely dependent on the type of tumor and its location. Some tumors grow very fast and are inoperable due to the cell type and location, and these patients have a poor prognosis. Other brain tumors can be lived with for years, or quickly and easily treated with surgery.

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Source: http://www.dailyrx.com/news-article/neuroblastoma-responds-combination-medications-19946.html

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