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Promising cancer drug aces human clinical trials

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A new cancer drug known as BLU-667 has moved through phase I human trials, and the results are promising. Taken orally, the drug targets what are known as RET-driven cancers, including types of thyroid and lung cancers, which are normally hard to treat.

RET is a type of receptor tyrosine kinase, and mutations that kick its activity into overdrive are linked to certain kinds of cancer. Among others, RET plays a role in around 50 percent of medullary thyroid cancers, 20 percent of papillary thyroid cancers, and up to two percent of non-small cell lung cancers. These can be treated with conventional methods, although so far success hasn't been stellar.

"There is a critical un-met need for effective drugs against cancers that have the RET alteration, as there are no highly potent inhibitors currently approved specifically for these RET-driven cancers," says Vivek Subbiah, lead researcher on the study. "The current treatments for these cancers are limited to traditional chemotherapy and earlier generations of multiple kinase inhibitors. These options have had limited success with often considerable side effects that significantly impact the patient's quality of life."


BLU-667 works by inhibiting the activity of RET, and it was chosen for further study after it was found to be 100 times more selective for RET, meaning it shouldn't affect the functions of other kinases. It's also been shown to prevent certain genetic mutations that may allow the body to resist this kind of treatment.

For this trial, the team studied 43 patients with advanced tumors that weren't able to be operated on, as well as 26 patients with medullary thyroid cancer, 15 with non-small cell lung cancer, and two with other RET-related cancers. The results were promising, with the researchers saying that BLU-667 seems to be effective and safe for use.

"Tumor reductions and durable responses were observed in most patients, especially those patients whose cancer progressed with chemotherapy and multi-kinase inhibitors," says Subbiah. "Our study reported an overall response rate of 37 percent for RET-driven cancers, with responses of 45 percent for non-small cell lung cancer and 32 percent for medullary thyroid."

The results of the trial were published in the journal Cancer Discovery, and presented at the American Association for Cancer Research Annual Meeting 2018 over the weekend.

Source: University of Texas MD Anderson Cancer Center


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