A modified version of a sea sponge protein fights cancer in mice without the side effects associated with existing chemotherapy. If the success is translated to humans it could offer relief for millions of cancer patients every year.
Cancer cells' capacity to divide, and therefore multiply, exceptionally rapidly is what makes them dangerous, allowing them to take over the body. However, this also provides a point of vulnerability, which chemotherapies exploit, targeting cells in the process of division. Unfortunately, cells the body needs, particularly those that also divide more rapidly than most, get damaged in the process, with side effects that can sometimes be devastating.
The class of chemotherapy drugs known as microtubule-targeting agents (MTAs) have frequently proven effective against cancer, but the microtubules they bind to are essential components of neurons, and the MTAs don't discriminate. The result can be neutropenia (a weakening of the immune system) and peripheral neuropathy (damage to the nervous system outside the brain and spinal cord).
Dr Michal Wieczorek of McGill University, Canada, has trialed DZ-2384, a compound that also targets cell microtubules, but does it in a fundamentally different way to existing MTAs. In Science Translational Medicine Wieczorek reports that application of DZ-2384 to mice with pancreatic and colon cancers left all mice free of tumors three months after treatment. Two out of four mice treated in the same way against lung cancer were also cleared of their tumors. Cancer cell concentrations were dramatically reduced in all eleven mice with acute lymphocytic leukemia treated in this way.
Most significantly, no signs of nerve damage were observed, even at concentrations well above those needed to get cancers under control.
DZ-2384 is a synthetic chemical, but one whose shape is based on Diazonamide A, a chemical released by Diazona angulata sea sponges. You don't hang around for 500 million years, as the sponges have done, without learning a thing or two about biochemistry, and the Diazona have provided us with a rich array of potentially useful compounds to explore. Some of these have proven hard to synthesize in commercial quantities, but Wieczorek and his co-authors state that this should not be a problem for DZ-2384.
Although DZ-2384 resembles MTAs in targeting microtubles, the paper reports it binds to its target “in a distinctive way that unexpectedly translates into superior antitumor efficacy and safety.” By changing the curvature of the protein tubulin, DZ-2384 straightens out the microtubular filaments, preventing cancerous cell division while having little impact on nerve cells.
As always with drugs that prove successful in animal models, it will be long years of clinical trials before DZ-2384, or any product based upon it, reaches widespread use among humans.
Untreated cancer cells in culture (left) compared to those treated with DZ-2384 (center) and a traditional MTA (right). The conventional MTA destroyed the microtubules entirely, while the DZ-2384 stunts them, but both effectively fight cancer. Wieczorek et al/Science Translational Medicine
