Sometimes, a part of one gene can be attached to another gene, creating a hybrid gene that often leads to malignancy. In pediatrics, a fused gene is frequent among rare cancer types, such as infantile fibrosarcoma. Researchers who are studying pediatric cancer developed a new drug that inhibits tumor caused by the said fused gene.

New Drug Combats TRK Fusions

The first case of the fusion gene was identified and described in cancer cells in the early 1980s. According to the European Society for Medical Oncology, a gene called tropomyosin receptor kinase was found in a small number of colon cancer cases in 1982. But in the years 2013 and 2014, more cases of the TRK gene were detected in other cancer types, such as in the lungs, breasts, and skin. The appearances of the TRK gene in modern cases have been associated with genetic fusion as well.

A research team from the University of Texas Southwestern Medical Center developed a new drug called Larotrectinib, designed to suppress the fused TRK gene. Larotrectinib belongs to a class of molecules called kinase inhibitors. These molecules target the mechanism of one or more protein kinases, making them effective in targeted therapy.

"In some cancers, a part of the TRK gene has become attached to another gene, which is called a fusion. When this occurs, it leads to the TRK gene being turned on when it's not supposed to be and that causes the cells to grow uncontrollably. What's unique about the drug is it is very selective; it only blocks TRK receptors," explained Dr. Ted Laetsch, the lead author of the study and an assistant professor of pediatrics at UTSW Medical Center.

TRK fusions only happen in a small number of cancer cases in adults, but it is recurrent in rare cancer types among children. The most common treatments for rare pediatric cancer include resection and chemotherapy. But if the tumor grows back and no possible treatments are available, the child would be in danger, such as in the case of Briana Ayala of El Paso.

Briana was diagnosed with a rare tumor inside her abdomen that wrapped around her aorta. Surgeons elected surgical intervention to remove the tumor in the largest vein of the human body. The procedure had removed the abnormal growth and a part of the tumor attached to the aorta. Unfortunately, the tumor returned and doctors have no other effective treatments to offer.

The resected tumor was sent by Dr. Laetsch for genetic testing and tests showed that the abnormal tumor cells have TRK gene fusion. The patient was enrolled in a phase I clinical trial of the new drug. Briana took the medication twice a day and has been relieved of symptoms, such as diminished pain and swelling in the abdomen, within weeks. Imaging tests also showed that the tumor significantly shrunk. For two years, Briana's health has improved with the new drug.

"These are the kind of amazing responses we've seen with larotrectinib. And this is why I'm so excited about it," added Dr. Laetsch.

Larotrectinib only targets the activation of the TRK gene fused in other genes, which means it can also be used to treat TRK fusion-related cancers of the lungs, breasts, colon, and thyroid. Researchers also analyzed the drug's efficacy in adult patients and found that it has a 75 percent response rate. The medication also has a long-lasting effect and causes only minor side effects, which prevents patients from quitting the trial.

The research team is planning to start a new clinical trial that involves patients who have developed resistance to another drug, similar to larotrectinib.

Cancers with TRK Gene Fusions

The TRK gene is important to the body, particularly in the brain and the nervous system. It is more relevant in the development of the nervous system in childhood and becomes a limited functional gene in adulthood, such as pain regulation. But any changes or mutations that can lead to genetic fusion result in cancer growth.

Three among several rare pediatric cancer types have TRK fusion, which are:

1. Infantile fibrosarcoma: It is a cancer type in children under one year of age, characterized by a tumor growth in the soft tissue, such fats, muscles, and nerves. The disease progresses slowly with the tendency to be benign, compared to fibrosarcoma in older children.

2. Cellular congenital mesoblastic nephroma: It is a cancer type that develops in the kidneys of younger children, including infants. The disease contributes to only five percent of all renal tumor cases among children, but it is the most common type of renal pediatric tumor among infants.

3. Papillary thyroid cancer: It is the most common type of thyroid cancer with a 10-year survival rate of more than 90 percent, in all cases. It is a rare disease among children less than 10 years old, but more common among children 15 to 19 years old.

[메디컬리포트=Ralph Chen 기자]