BOSTON The nanopharmaceutical drug CRLX101 is showing promise as a potential new treatment for cancers that develop resistance to antiangiogenic drugs and radiation therapy, according to clinical trial results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19 23.
Antiangiogenic drugs are anticancer drugs designed to cut off the blood supply that brings tumors the nutrients they need to grow and survive, thereby starving and killing the tumor cells. Over time, however, tumors usually develop resistance to these drugs, often because of the upregulation of a protein called HIF-1 alpha. This protein promotes tumor invasion, metastasis, and cancer stem cell formation, all of which make tumors more aggressive and unmanageable. Antiangiogenesis drugs, as a result, have achieved limited success in the treatment of cancers.
"Reducing or eliminating resistance to antiangiogenic drugs could have meaningful implications for cancer patients. Up until now, HIF-1alpha has been considered impossible to target safely, but CRLX101 may change that," said Scott Eliasof, Ph.D., vice president of Cerulean Pharma Inc., in Cambridge, Mass. "CRLX101 has been shown to inhibit HIF-1alpha, and the clinical data we have obtained to date suggest that it has limited side effects, which may permit it to be effectively combined with other drugs. We believe that CRLX101 may have the potential to manage resistance to antiangiogenic and radiation therapies.
"Based on our preclinical data, we believe CRLX101 may have the potential to have a significant effect on pathological complete response in rectal cancer patients and on overall survival duration in patients with ovarian and kidney cancers," he added.
CRLX101's payload is the toxic anticancer drug, camptothecin, chemically conjugated into nanoparticles of 20-30 nanometers in diameter, using polymeric materials. When CRLX101 is taken up by the tumor
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American Association for Cancer Research