New paper: The next genetic revolution in cancer treatment?

While there have been huge advances in cancer treatment in recent years, far too many solid tumours and blood cancers remain untreatable. Sygnature’s director of oncology drug discovery, Dr Allan Jordan, has published a ‘call to arms’ to the drug discovery and clinical communities in the British Journal of Cancer. He speculates that more, and better, cancer treatments might be found if discovery scientists and clinicians worked together more closely.

The approval of Novartis’s imatinib (Gleevec) back in 2001 ushered in a new era for cancer therapy. It was the first time that a specific genetic mutation within cancer cells had been targeted successfully, and provided the first effective treatment for chronic myelogenous leukaemia. This represented a huge advance on non-selective cytotoxic chemotherapy drugs, raising the prospect of being able to kill cancer cells without damaging healthy ones.

Since then, numerous other targeted cancer drugs have reached patients. Personalised medicine, where the drug is chosen based on disease genetics, is already proving a game-changer for some patients. It now costs less than $1000 to decipher the genetics of a tumour or blood cancer, and many key specific mutations can already be paired up with targeted drugs. Melanoma is just one example of a ‘difficult’ cancer that can now be treated – if the cells have the right mutation.

Yet, in practice, we remain a long way from being able to treat all – or even most – cancers in a genetically determined way. Today, only about 5% of patients benefit from the approach. For many others, their cancers simply don’t have a genetic profile that we understand. Even if they do, there is a good chance there is still no drug that specifically targets an identifiable mutation.

What should we be doing to find treatments for these patients? The answer may well lie in a closer collaboration between drug discovery scientists and their clinical colleagues, looking more deeply at those patients whose cancers are genetically unsuitable for either existing drugs or planned clinical trials. If we considered their genetics a little differently, we might be able to discover new cancer drug targets and medicines that would benefit more cancer types, and deliver another step-change in patient care.

Would you like to read on?  We have made Allan’s BJC paper on the topic ‘open access’ so everyone can have a read, check it out:

Jordan, AM (2021) Molecularly profiled trials – toward a framework of actions for the “nil actionables”, British Journal of Cancer.