New Study Manages To Prevent Neuroblastoma Resistance To Crizotinib

New Study Manages To Prevent Neuroblastoma Resistance To Crizotinib

Researchers have discovered a new therapeutic combination to prevent resistance of neuroblastoma to crizotinib. Researchers work at The Institute of Cancer Research in London on neuroblastoma treatment was succesful. The study, led by The Institute of Cancer Research in collaboration with the Dana-Farber Cancer Institute and Children’s Hospital in Boston, shows that the new combination therapy had positive results in the first stage of trial.

Neuroblastoma, along with nephroblastoma, is one of the most solid solid tumors of child. Neuroblastoma derives from cells which originate in neural crest. Neuroblast cells  are cells that develop peripheral sympathetic ganglion neurons. It must be said that neuroblastoma is the most common malignant tumor diagnosed in the first month. Depending on the genetic component (n-myc), there are forms of neuroblastoma more aggressive or less aggressive. Symptoms caused by neuroblastoma differ depending on where the tumor size, extension, etc.. The most common sign is the  increase of abdomen. On palpation, the tumor shows features of a malignant tumor: firm, irregular surface, reinforcing the deep plans. Depending on the extension, neuroblastoma can cause spinal cord compression with neurological manifestation. In case of metastasis, the child may have hepatomegaly. Metastases may be present not only in the liver, but the eye or skin. Also, if the adrenal gland is involved, catecholamines secreted will cause hypertension. An important role is played by imaging diagnosis (MRI or CT) and exploration biochemical (urinary excretion of vanilla mandelic acid, metabolite of catecholamines).

Crizotinib Pills

Researchers have tried to prevent the emergence of resistance of  neuroblastoma by combining mTOR inhibitors with crizotinib. Crizotinib is a drug used to treat non-small cell Lung Carcinoma (NSCLC), approved by the FDA. It acts as ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor. Although the cancer initially respond to crizotinib, subsequently ALK mutations occur in cancer cells and they become  resistant to treatment.

Now, due to combination with mTOR inhibitors crizotinib, researchers have found a solution to prevent the occurrence of cancer resistance. They hope that this combination therapy proved to be useful in other cancers, not only for neuroblastoma. mTOR (mammalian target of rapamycin (mTOR) protein kinase is actually a kinase protein rsponsible for cell division, transcription, cell motility and protein synthesis. Triggering PI3K/AKT/mTOR pathway is involved in the development of certain cancers, neuroblastoma, but also in certain adult cancers
After discovery, the researchers realized that neuroblastoma becomes resistant to crizotinib  by turning on the PI3K/AKT/mTOR pathway. Therefore, by inhibiting mTOR researchers could overcome the  tumor resistance to crizotinib.