Study exposes Achilles heel of deadly kidney cancer

The red dots represent the protein complex in kidney 

cancer cells that spur cancer growth. The right frame 

shows tumor after treatment with PT2385

CANCER DIGEST – Feb. 22, 2020 – An experimental drug already shown to be safe and helps some patients with a deadly form of kidney cancer, has shed light on a possible new way to treat the cancer.

“Short of a cure, which we’re still struggling to get to patients, we think this drug and other future drugs in this class could offer a durable way to fight this cancer while preserving quality of life,” said Kevin Courtney, M.D., Ph.D. in a press release.

The University of Texas Southwestern Medical Center associate professor of internal medicine (hematology/oncology) led a team of researchers at the UTSW published their findings in the Feb. 15 issue of Clinical Cancer Research.

About 70,000 new cases of clear cell renal cell carcinoma (ccRCC), a particularly deadly form of kidney cancer, are diagnosed every year in the U.S. The five-year life expectancy after diagnosis is low compared with other cancers, at about 10-12 percent, in part because the cancer doesn’t respond to chemotherapy or radiotherapy.

Research has shown that the tumor produces a pair of proteins that bind together to regulate the expression of over 100 genes, including many that play key roles in cancer, such as those that control the formation of blood vessels or maintain stem cell-like qualities, which allows the tumor to continuously reproduce its cells.

Out of that earlier research investigators developed a drug, called PT2385 that blocks the protein combination the tumor needs to accelerate growth. A phase one clinical trial showed that this compound was safe, well tolerated, and effective at controlling cancer in 40 percent of patients.

Through an in-depth study of a subset of those patients who were willing to undergo extensive testing, the investigators sought to determine how well PT2385 blocked the protein combination in ccRCC patients. Their results showed that within two weeks after patients started on the drug, the amount of blood circulating in their tumors decreased by about 29 percent on average.

Within tumors, tests on biopsied tissue showed that PT2385 effectively dissolved the protein complex blocking the activation of cancer-promoting genes.

Unfortunately, after more than a year on PT2385, patients’ tumors appeared to develop resistance to the drug, and resumed progression. Still it gives researchers a clear indication that they are on the right track for developing an effective drug for this cancer.

Sources: press release from UTSW Medical Center, and the journal of Clinical Cancer Research