07:19am Wednesday 13 December 2017

A less toxic approach to beating cancer

A cocktail of non-toxic doses of chemicals taken from food and vegetables may be key to tackling untreatable cancers and disease relapse, according to the findings of a global study jointly led by Cardiff.

Despite a number of advances, many cancer therapies are highly toxic, and even when they appear to work, a significant percentage of patients will experience a relapse after only a few months. 

Typically these relapses result from small subpopulations of mutated cells which are resistant to therapy, and doctors who try to address this problem with combinations of therapies find that therapeutic toxicity typically limits their ability to stop most cancers. 

To tackle this problem, a task force of 180 scientists from prominent institutions in 22 countries, including Wales, was assembled by a Canadian NGO called “Getting to Know Cancer”.   Interdisciplinary teams nominated a series of high-priority molecular targets (74 in total) that could be reached with chemicals to improve patient outcomes in most cancers.

Corresponding low-toxicity chemical approaches were then recommended as potential candidates for mixtures of chemicals that could reach a broad-spectrum of priority targets in most cancer types.  Their work is described in a special issue of Elsevier’s ‘Seminars in Cancer Biology’, published today.

Keith I. Block, MD, the lead-author of the paper, who is the Medical and Scientific Director of the Block Center for Integrative Cancer Treatment in Skokie, Illinois, said: “We are extremely encouraged by the degree of consensus that we found within this large group of researchers. 

“We believe that carefully designed combinations of non-toxic chemicals can be developed in a manner that will maximize our chance of arresting most cancers.  Currently, clinicians have a limited number of tools to help them treat the disease once it becomes resistant to mainstream therapy, but an approach that can reach a broad-spectrum of targets without toxicity offers considerable promise.”

This was the first time that teams of researchers with such a wide range of expertise have ever been assembled to address the complex problem of relapse. The teams have emerged believing that carefully designed combinations of non-toxic chemicals can be developed that will maximize our chances of arresting most cancers.

A number of investigations on the low-toxicity chemicals were conducted by the Cardiff University arm of the research, who led on one of its key themes: cancer invasion and metastasis (spread).

Together with scientists from a number of other countries in North American, Europe and the Far East, the team identified a series of phytochemicals that are found naturally in plants which, when combined into a mixture, have the potential to intervene in metastasis – the leading cause of cancer deaths.

For example, Cardiff’s China Medical Research Collaborative (CCMRC) teamed up with Peking University, Capital Medical University and Yiling Medical Research Institute of China to study the cancer-fighting properties of a herbal medicine, known as YangZheng XiaoJi.They discovered that the medicine has the potential to intervene in cancer metastasis by targeting the formation of new blood vessels that support tumour growth, and a number of cellular signalling pathways in cancer that has not yet spread.

Professor Wen Jiang, from Cardiff’s School of Medicine, said: “Traditional Chinese Medicines are an interesting avenue for novel cancer therapies, representing relatively low-toxicity and inexpensive formulations that have been in use for centuries.  Whilst research in cancer has progressed over past years, research into compounds to prevent metastasis – a process associated with poor patient prognosis – are relatively lacking. 

“Our research on YangZheng XiaoJi has explored the efficacy of this formulation in targeting aggressive pro-metastatic traits in a variety of human cancer models.  We found that YangZheng XioaJi could disrupt the ability of cancer cells to adhere and migrate and interfere with a number of signalling pathways associated with cancer progression. 

“Additionally, this formulation was shown to interfere with the process through which cancer cells encourage new blood vessel formation to obtain nutrients necessary to sustain their development. Hence, this may represent a low toxicity formulation capable of targeting multiple aspects of cancer progression.”

Whilst the molecular basis of the medicine is further investigated, a number of clinical trials are now ongoing in China in patients who suffer from lung, liver, and gastric cancers.

In light of this evidence, the task force is calling for an immediate increase in support for research on mixtures of chemicals that can reach a broad-spectrum of therapeutic targets.  There are still many unanswered questions so animal trials are now needed to advance this approach before human trials are possible. 

“This is an area that merits considerable attention,” said Dean Felsher MD PhD, another team leader on the taskforce, from the Department of Medicine at Stanford University.  “Our approaches to therapy are improving, but we need a breakthrough that can help us address the problem of relapse, and this is a new, paradigm-changing approach that might just give us a chance”, he added. 

The taskforce also want to produce an approach to therapy that would have the potential to be very low cost, because many of the latest cancer therapies are deemed unaffordable in low-to-middle income countries. 

Accordingly, the task force has laid the groundwork for a solution that should be both inexpensive and effective in making this novel approach available to people throughout the world who are suffering from cancer.

Cardiff University.


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