Astellas taps UK scientists for pancreatic cancer leads

Astellas has joined forces with medical researchers in the UK to develop therapies that – somewhat counter-intuitively – stop pancreatic cells eating themselves.

The research project – conducted alongside Cancer Research UK – is focusing on a remarkable process in pancreatic cancer and certain other malignancies known as autophagy, from the Greek for ‘self-eating’.

By breaking down some cancer cells, more nutrients are available to feed growth in the remainder of the tumour, so the process acts as a survival mechanism when a cancer starts to outstrip its nutrient supply. Moreover, tumours also use autophagy to outwit cancer treatments, with some cells sacrificed to help the rest cope with the stress of chemotherapy.

Autophagy is a normal cellular process but seems to be permanently switched on in pancreatic cancer, which is thought to be one reason why it is so malignant. Typically, the median survival after diagnosis for pancreatic cancer is just six months, and only around three per cent of patients in the UK survive beyond five years.

Astellas, Cancer Research UK and the medical charity’s commercial arm Cancer Research Technology aim to identify and validate new drug targets that block autophagy in pancreatic cancer cells, with the Japanese drugmaker claiming an exclusive license to advance the most promising candidates through drug discovery and development.

The primary research will be carried out by Professor Kevin Ryan at the Cancer Research UK Beatson Institute and Dr Sharon Tooze at the Cancer Research UK London Research Institute and will focus on developing drugs that can block autophagy and complement the effects of chemo- and radiotherapy.

It has been recognised for some years that autophagy can be blocked in cancer using drugs in the chloroquine class, and in May researchers from the University of Pennsylvania in the US reported a series of early-stage clinical trials which suggested hydroxyquinone could have a therapeutic effect in several cancers.

For example, in melanoma, the researchers observed prolonged stable disease in 20 per cent of patients treated with temozolomide. In another melanoma trial, researchers observed stable disease in 75 per cent of patients on temsirolimus.

There are currently more than 40 clinical trials involving hydroxyquinone as a potential autophagy inhibitor in cancer, according to UPenn researcher Ravi Amaravadi, who is leading the project.

Hydroxyquinone could provide a cheap and plentiful autophagy inhibitor if its early potential is borne out in later-stage trials, but in the meantime Astellas and other pharma companies are trying to identify the pathways involved in blocking the process and develop more potent and selective drug candidates.

The collaboration is the first between Cancer Research Technology and a Japanese pharmaceutical company and will combine the UK charity’s “world-leading target validation expertise and Astellas’ proven track record on drug development,” said the partners in a joint statement.

Astellas’ chief strategy officer Kenji Yasukawa said the alliance stemmed from a programme initiated at the company last year in which it “invited researchers from around the world to collaborate to increase drug discovery opportunities and expand development pipelines.”



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