Researchers at MD Anderson Cancer Center, the University of Texas, have discovered the mode of action of new anti-cancer drugs called imipridones in treating blood cancers, such as mantle cell lymphoma and acute myeloid leukemia (AML).
The study majorly focused on caseinolytic protease P (ClpP) in mitochondria. The activation of ClpP stimulates the process of mitochondrial proteolysis, in which breakdown of proteins occurs within mitochondria. A novel class of anti-cancer drugs, called imipridones, is capable of activating ClpP that ultimately leads to cancer cell death through mitochondrial proteolysis.
The anti-cancer drugs, ONC201 and ONC212, act irrespective of the form of the common tumor suppressor p53. The study findings are recently published in the journal Cancer Cell.
Through in vitro and in vivo trials, the researchers confirmed that in the case of inactivated mutant ClpP gene, both ONC201 and ONC212 drugs were ineffective, demonstrating that ClpP activation is essential for imipridones-induced cell death. With the help of extensive crystallographic techniques, the researchers observed the structure of ClpP and discovered the precise binding sites and binding patterns of the drugs on it. They also revealed the mechanism behind increased protease activity.
On a similar note, researchers at the University of California, Los Angeles (UCLA) are trying to combat the adverse effects of oral surgery, such as jawbone damage in case of cancer patients or osteoporosis.
Currently, doctors and surgeons prescribe bisphosphonates for patients suffering from osteoporosis or bone cancer to avoid the extensive loss in bone density. However, an overdose of this drug during oral surgical treatment can cause chronic pain, infection, and inflammation, which possibly lead to the destruction of jawbone tissue.
In pre-clinical trials, researchers from UCLA and USC were able to replace bisphosphonate drugs collected around the jawbone by injecting inert bisphosphonate compound that does not have any pharmacological effects. This technique would allow the bisphosphonate drugs to act normally on the rest of the skeleton, preventing the extensive bone loss.