Playing a blocking game against tumors
LEIDEN, The Netherlands—United Kingdom-based Cancer Research Technology (CRT) and the Institute of Cancer Research (ICR) have tapped Dutch drug discovery company ZoBio BV in an effort to discover and develop drugs to block a DNA repair target which may play a role in cancer cell survival.
Financial terms of the three-way deal remain under wraps, but in terms of general aspects of the deal, CRT will manage commercialization arising from any potential drug compounds discovered through the collaboration. In addition, CRT—which is the commercial arm of Cancer Research U.K.—will share a portion of future revenues with ZoBio and with the ICR, which is a college of the University of London.
According to CRT, the collaboration will combine the ICR's expertise in drug discovery and target validation with ZoBio's patented drug fragment screening technology—its Target Immobilised Nuclear Magnetic Resonance Screening (TINS) platform—to identify small molecules that bind to and block the DNA repair target.
According to ZoBio, TINS is a proprietary technology that combines "the robust nuclear magnetic resonance (NMR) imaging approach with extreme sensitivity to very weak interactions such as those between a drug fragment and a target."
As the partners note, DNA damage occurs during each cell division. If DNA damage is allowed to accumulate, cells will stop dividing and may eventually die. Healthy cells use several different routes to identify and repair DNA damage, but cancer cells on the other hand, which divide rapidly and accumulate more DNA damage, often have faults with a major DNA repair process.
Because of this, tumors are forced to rely on what the partners call "back-up routes" and the potential drugs they envision coming out of this collaboration would block one of the remaining alternative repair routes, thus causing DNA damage to quickly mount in cancer cells until they are overwhelmed by it.
In addition, the trio of organizations also anticipates that such drugs would boost the effectiveness of many forms of chemotherapy, as the compounds used in such therapy do their job by damaging cancer cells at a rate faster—ideally, at least—than the cancer cells can repair themselves.
Healthy cells could tolerate the type of drug CRT, ICR and ZoBio envision because they divide more slowly and retain their main repair machinery which provides effective DNA repair, according to Dr. Phil L'Huillier, CRT's director of business development, who adds: "Cancer Research U.K. and the ICR have already made strides in breast cancer treatment by blocking two DNA repair routes at once. People missing the DNA repair protein BRCA can be treated with a drug blocking PARP, an enzyme on a different DNA repair pathway. This approach is delivering impressive clinical trial results, which could lead to better survival. We hope that similar drugs identified through the collaboration could also have promising results, ultimately increasing survival from a range of cancers."
"We are excited to work with the ICR on such an exciting and novel target," says Dr. Gregg Siegal, chief scientific officer of ZoBio. "We are convinced that we can provide valuable starting matter through the use of TINS where other approaches have failed."
Also providing a level of excitement for ZoBio and boosting confidence in its abilities was the news about a week after the CRT/ICR announcement that two Big Pharma companies have extended collaborations with ZoBio.
Johnson & Johnson Pharmaceutical Research & Development, a division of Janssen Pharmaceutica NV, for one, has extended its collaboration with ZoBio to include fragment discovery services on two new targets. These new efforts come on top of ongoing fragment discovery and NMR-based structural biology services on target-ligand complexes ZoBio is already providing to J&JPRD.
In addition, GlaxoSmithKline PLC has extended its collaboration with ZoBio to include fragment discovery on a new target as well as NMR-based structural biology on target-ligand complexes for an ongoing drug discovery campaign.
In the official news release about those extensions, ZoBio officials noted that they are "proud that such a high percentage of our customers come back for new projects and new services. This repeat business is a clear validation of our customer-centric philosophy."