Secondary breast cancer happens when sleeping cancer cells (too small to see on a routine scan) start to grow in other parts of the body, and this can happen 10-20 years later. Many of the deaths from breast cancer are due to the ability of these new cancer deposits to mutate and transform and develop resistance to the drugs available. When the last drug stops working, there are no more options left. The team of breast surgeons, oncologists and scientists at Imperial College London led by Dr Suzy Cleator, Prof Charles Coombes and Prof Simak Ali is trying to work out what the mechanisms are that cause drug resistance, tumour regrowth and metastatic spread.
Once these mechanisms are identified, the team at Imperial College London hopes to develop simple blood tests to pick up metastatic spread or drug resistance at a much earlier stage. The team is currently designing clinical trials to test the usefulness of these “liquid biopsies” for tailoring patient treatments. Breast cancer is a not a ‘one-size-fits-all’ disease, so secondary cancer patients respond differently to the same treatment, depending on which type of breast cancer they have, and how many organs are involved. By individualising cancer therapies, patients will only get the treatments most likely to benefit them, which should improve their quality of life by getting rid of ineffective drugs and their associated side effects.
The work of the Imperial team has also led to the identification and clinical assessment of new cancer drugs to treat therapy-resistant breast cancer. They enlisted the help of scientists from the other disciplines at Imperial College, including chemists, pharmacologists and structural biologists, forming the Imperial College Cancer Drug Design and Development Group. This interdisciplinary group has been able to rationally evaluate discoveries from the cancer laboratories for potential as new cancer treatments.
One of the treatments they have developed is called ICEC0942, which entered clinical trials at the end of 2017. The results are eagerly awaited. This drug targets an enzyme called CDK7, involved in directing cells through their lifecycle, which consists of growth, DNA replication and cell division. CDK7 is also critical for the process of transcription, a vital step in gene expression – the creation of proteins to carry out cell functions. Particular cancers, such as treatment-resistant breast cancers, have a unique dependence on transcription, meaning targeting CDK7 may be particularly effective.
By inhibiting transcription, ICEC0942 shuts down the ability of the cancer to spread. As well as breast cancers, cancers such as acute myeloid leukaemia and small-cell lung cancer are particularly transcription-dependent and evidence from the laboratory indicates that ICEC0942 will work well for these too, especially where they have become resistant to other treatments.