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Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive cancer affecting the brain or spinal cord, primarily in children under the age of 3. However, older children and adults can also be affected. AT/RT's challenging nature is underscored by its association with a genetic alteration leading to a loss of the SMARCB1 protein function, delineating into three subgroups based on tumor location, age at diagnosis, and specific genetic changes. Despite current treatments involving intensive chemotherapy, the prognosis for AT/RT remains dismal, with high toxicity and poor outcomes, driving the need for more effective and tolerable therapeutic options.
At Children's Hospital Colorado, Jean Mulcahy-Levy, MD, and her team embarked on a quest to unveil new treatment avenues using a CRISPR genetic screen. Their research spotlighted CDK7, a crucial enzyme overexpressed in AT/RT, as a potential therapeutic target. Through rigorous testing, including a CDK7 inhibitor in a mouse model of AT/RT, they observed a significant vulnerability in tumor cells upon inhibition. However, the quest didn't stop there; further investigation revealed a potent combination therapy involving a CDK7 inhibitor and methotrexate, an antimetabolite known for its use in chemotherapy. With CDK7 inhibitors, like oral samuraciclib, proving safe in adult trials, there's hope for their application in pediatric AT/RT treatment.
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