New type of cancer drugs on the way
Researchers from the Vanderbilt Medical Center have discovered a collection of compounds that could represent a new class of drugs for treating cancer. The compounds are actually selective inhibitors of the protein phospholipase D (PLD), an enzyme that has been implicated in multiple human cancers including renal, breast, and gastric.
These newly found compounds stop the invasive migration of breast cancer cells, supporting their further development as antimetastatic agents.
“PLD is associated with many fundamental cellular processes like secretion, migration, growth and proliferation. But the absence of selective inhibitors has really interfered with the ability of biologists to study this important enzyme,” said Alex Brown, one of the researchers.
There are actually two forms of the enzyme — PLD1 and PLD2. Both of them produce phosphatidic acid, a key lipid metabolic and signaling molecule. Now, scientists from VICC discovered that PLD was important to the invasive migration of breast cancer cells in culture using a genetic tool called small interfering RNA (siRNA).
“When we had evidence from siRNA and other methods that blocking PLD resulted in dramatic effects of blocking metastatic invasion of breast cancer cells, we were highly motivated to attempt to make isoform-selective inhibitors,” said Brown.
Craig Lindsley, another scientists who worked on this project said: “With the compounds we’ve made, we can almost choose the range at which we’d like to inhibit the different isoforms, something that’s never before been possible.”
The scientists will now try optimize their new compounds for in vivo studies and to give them characteristics compatible with being good medications.
The details are published in the journal Nature Chemical Biology.
Source: vicc.org
