“Three solutions to cancer’s drug resistance” – Professor Paul Workman visits China

Earlier this week our Interim Chief Executive Professor Paul Workman made the trip to Beijing to speak at a prestigious ‘Hallmarks of Cancer’ symposium run by the publishers of the journal Cell, one of the world’s leading scientific journals. The conference took a global perspective on cancer – which is the leading cause of death in China.

Professor Workman used his invited talk to lay out some of the main, overarching challenges researchers need to tackle in order to find new treatments for cancer. The main challenge we face, Professor Workman said, is to prevent or overcome drug resistance. The “survival of the nastiest” cancer cells, driven by Darwinian evolution, is the reason why cancers become resistant to treatments – the reason, ultimately, why so many people worldwide still die from cancer.

The scale of the challenge posed by drug resistance is enormous – comparable with the challenge of antibiotic resistance in infectious disease, which is also driven by Darwinian evolution.

Three solutions to drug resistance

In Beijing, Professor Workman gave three possible solutions to the challenge of drug resistance in cancer.

• “Expanding the druggable cancer genome”. Although around 500 cancer-causing proteins are known, drugs that target them exist for only about 5 per cent of them – an issue covered recently in greater depth in Professor Workman’s own blog. Researchers in academia and industry need to focus more effort on currently untargeted cancer proteins, rather than developing ‘me-too’ drugs which simply mimic the effects of existing drugs. In collaboration with industry partners, at the ICR we are developing drugs against several new cancer targets, including the protein Chk1 and members of the WNT signalling pathway.
• “Discovering and implementing the best targets for drug combinations”. Some drugs will work more effectively when combined with others – in combination, drugs can cut off the evolutionary escape routes used by cancer to find new ways to grow and spread. ICR researchers are exploring different drug combinations in the laboratory – and our clinical scientists, in collaboration with our partners at The Royal Marsden and other UK hospitals, are currently trialling several different combinations of drugs against different cancer types to overcome drug resistance.
• “Discovering cancer network medicine drugs to overcome or prevent resistance to targeted agents”. Network drugs tackle more than one of the cellular signalling pathways that are hijacked in cancer. These drugs can hit cancer harder than drugs targeted to only one protein, because they can hit several targets at once. It will be particularly exciting if we can identify genes that are involved in the actual process of cancer evolution and to target these for therapy. One network drug example is AUY922, which targets a protein called HSP90, and was discovered by ICR researchers in collaboration with partners, and is now undergoing late-stage clinical trials for different cancer types.

Team science

Underpinning all of these approaches, Professor Workman said, is the need for collaboration – within individual research centres like the ICR, with clinical partners, with other academic institutions, and with industry. Professor Workman ended his talk with an urgent call for increased collaboration to bring more new treatments for patients, more quickly – pointing out that “drug discovery is a team sport”.