New cancer drugs show great promise

CDKI-73 and MKI-18 may sound like characters from Star Wars or a Cold War spy novel, but their background is even more intriguing and their impact could be very significant.

Research at UniSA has highlighted their potential to kill cancer cells without having too much impact on surrounding normal cells – one of the holy grails of cancer research.

Trials are still continuing but the signs are positive, and the icing on the cake is that both could be given orally rather than by injection, making them easier for administration. “They could even take them home, avoiding the need to spend so much time in hospital,” said Professor Shudong Wang, who leads the multidisciplinary research team.

CDKI-73 is one of the most developed pre-clinical drug candidates the team is studying, and it has shown signs of being particularly efficacious against chronic lymphocytic leukaemia, acute myeloid leukaemia, and cancers of ovarian, colorectal and prostate.

CDKI-73 targets cyclin-dependent kinases (CDKs), the proteins that promote cancer cell proliferation and survival. Targeting CDKs has been seen as one of the most promising anti-cancer strategies since these proteins were discovered by Paul Nurse and Tim Hunt, who won the 2001 Nobel Prize for their work.

In recent years Professor Wang’s team in the Sansom Institute’s Centre for Drug Discovery and Development has been at the forefront in the race to target CDKs, after a particular CDK, CDK9 was identified as an important kinase, that is involved in cancer, HIV and cardiac hypertrophy.

MKI-18, another drug candidate developed by Professor Wang’s team, targets the Ras-Raf pathways by binding to the Ras-binding domain that is associated with various cellular proteins. Ras-binding events of these proteins are known to drive the development and maintenance of many cancers. MKI-18 mimics Ras and interferes with Ras-driven oncogenic signals in cells, and thus effectively kills cancer cells.

The Centre has capabilities spanning drug design, medicinal chemistry, biology and pharmacology and a mission to speed up the drug development process.

“We use targeted therapy where you identify the proteins or genes that are critical for cancer cell proliferation and survival, but dispensable for ‘normal’ cells” Prof Wang said. “We then design small-molecule drug compounds to block the production or action of those genes or proteins, resulting in cancer cell death.”

“When we target those genes or proteins, the compounds are more likely to be less toxic to normal tissues so they are quite different to conventional chemotherapy, which kills both cancer cells and ‘normal’ cells. This is a huge advancement for cancer treatment.”