Direct activation of a tumor suppressor protein by a new small molecule can prevent the growth of lung cancer

In a new study, researchers found that using a new small molecule to directly activate a tumor suppressor protein can prevent the growth of lung cancer in mice Dr goutham narla, of Case Western Reserve University in the United States, said, "all the drugs we currently have (http:// to treat our cancer patients are targeted kinases, the enzymes that phosphate molecules attach to proteins But just as important as this is the presence of an enzyme (phosphatase) that removes phosphate molecules " A phosphatase called PP2A can shut down the expression of tumor proteins by removing phosphate molecules attached to them But, according to Dr narla, "the expression of this tumor suppressor protein is turned off in almost every major cancer Its inactivation is essential for a normal cell to become a cancer cell " Narla and his team decided to take an unconventional approach to cancer drug development: looking for molecules that directly target PP2A to reactivate its tumor suppressive properties 54 researchers worked together to screen whether a series of drug like molecules could reactivate PP2A in lung cancer cells and prevent the growth of lung cancer tumors in mice The researchers found that a specific prototype drug could attach to a subunit of PP2A protein, effectively activating the enzyme As Dr narla explained, the study is the first to use a small molecule to directly activate an enzyme that removes phosphate molecules In laboratory models (including preclinical lung cancer cell models and mouse models), the prototype drug also blocks the proliferation of lung cancer cells Mice injected with the prototype drug had fewer lung cancer tumors and did not experience weight loss or behavioral abnormalities associated with other cancer drugs In mouse models, the efficacy of the prototype drug can be comparable to the current combination of drugs used to delay the progression of lung cancer To confirm where the prototype drug binds to PP2A, the researchers also created lung cancer cells with specific mutations at the putative drug binding site Mice with tumors produced by these mutated lung cancer cells did not benefit from the prototype drug because it was unable to bind and reactivate PP2A Narla noted that "there are about 2000 papers exploring the role of PP2A in cancer In breast cancer, prostate cancer, lung cancer, brain cancer, children's cancer, ovarian cancer and endometrial cancer, every major cancer involves the inactivation of this protein The molecules that allow us to activate its expression have the potential to play a role in a range of cancer patients " Narla added, "we are testing our prototype drug in a series of animal models If things continue to go well, we hope to use this prototype drug for clinical trials next year (http:// Our preliminary clinical trial will be more extensive and will cover many different types of cancer patients, including lung cancer patients " This study was carried out in preclinical lung cancer cell model and mouse model The results may not be applicable to human lung cancer In addition, mice received lung cancer transplants, rather than their own production of the tumor, and they received the prototype drug only for four weeks The long-term efficacy of the prototype drug is still unknown.