Discovery of ERK5 inhibitors for biomarker-driven clinical evaluation in cancer

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Cancer is now the commonest cause of death from disease in the UK, and increasingly in all developed countries. In the UK, prostate cancer is the most common malignancy in males, breast cancer the most common in females and, worldwide, liver cancer is the 3rd most common tumour type. Therapeutic options for the common cancers remain limited, and only drug therapy is of proven benefit for the management of metastatic disease, the primary cause of death in cancer patients. Although the range and activity of drugs available for cancer treatment are improving, over 150,000 patients still die of the disease in the UK each year. Hence there remains a substantial unmet clinical need, and ERK5 is an exciting new drug target in multiple tumours including prostate, breast and liver cancer.Selective and potent inhibitors of the signalling enzyme ERK5 will be developed and a clinical trial candidate and a back-up compound identified during the 2 year MRC DPFS award. Subsequently, the compound(s) will be evaluated in patients with cancer and the clinical development pathway for new cancer medicines is well-defined. Importantly, ERK5 inhibitors are representative of the new generation of targeted cancer drugs and hence a comprehensive portfolio of tests or biomarkers is essential for the optimal pre-clinical and clinical development of drug candidates, and their eventual use as stratified medicines - i.e. making sure that the right patient gets the right drug at the right time. These biomarkers will be developed alongside the drug candidate using invasive (biopsy) and non-invasive (imaging) technologies.The research output, a new drug in a new class, will provide an exciting new treatment option for patients with cancer. Furthermore, the co-development of biomarkers will allow the treatment to be directed towards those patients who are most likely to benefit, and allow the early evaluation of the therapeutic potential of ERK5 inhibitors.