OUR SCIENCE BIT....FOR GENERAL AUDIENCE

As you read this, millions of your cells are dying. Don't panic—you won't miss them. Most of them are either superfluous or potentially harmful, so you are better off without them. In fact, your health depends on the judicious use of a certain kind of programmed cell death—apoptosis. If you'd like to know more about these fascinating processes read more here >>

​

All the cells in our bodies are programmed to die. As they get older, our cells accumulate toxic molecules that make them sick. In response, they eventually break down, clearing the way for new, healthy cells to grow. This “programmed cell death” is a natural and essential part of our wellbeing. Every day, billions of cells die like this in order for the whole organism to continue functioning as it is supposed to.

But as with any programme, errors can occur and injured cells that are supposed to die continue to grow and divide. These damaged cells can eventually become malignant and generate tumours. In order to avoid their programmed cell death in this way, cancer cells reorganise their metabolism so they can cheat death and proliferate indefinitely.
​
Cancer researchers have known for decades that tumours use a faster metabolism than normal cells in our body. One classic example of this is that cancer cells increase their consumption of glucose to fuel their rapid growth and strike against programmed cell death. This means that limiting glucose consumption in cancer cells is becoming an attractive tool for cancer treatments.
In a study published in Nature Communications we showed that cancer cells stimulate the over-production of the protein known as PARP14, enabling them to use glucose to turbocharge their growth and override the natural check of cell death. Using a combination of genetic and molecular biology approaches, we have also demonstrated that inhibiting or reducing levels of PARP14 in cancer cells starves them to death. The best news is that by comparing cancer tissues (biopsies) from patients that has survived cancer and those that have died, we have found that levels of PARP14 were significantly higher in those patients that have died. This means that levels of PARP14 in cancer tissues could also predict how aggressive the cancer would be and what the chances are of a patient’s survival. This means that a treatment which could block the protein could represent a significant revolution in the future of cancer treatment. What’s more, unlike traditional chemotherapy and radiotherapy, the use of PARP14 inhibitors would only kill cancer cells and not healthy ones. Our work is aimed to design and generate new drugs that can block this protein and work out how to use them safely in patients.

​

More recently we have also been studying rare types of cancers. Bile duct cancer is a rare but aggressive form of cancer, affecting just over 2,000 people in the UK every year. However, incidences of bile cancer are steadily increasing every year – with some estimating it could one day be as common as breast cancer. In a major new study published in HEPATOLOGY our research group proposes that the drug all-trans retinoic acid (ATRA) could be used to help treat bile duct cancer.  ATRA is the active metabolite (small molecule) of vitamin A. ATRA is involved in cell differentiation (where one cell turns into a specific type of cell), and cell death. It’s also used to treat certain types of blood cancers – such as acute promyelocytic leukemia. Although using ATRA to treat this type of leukemia is well established and tolerated in patients, research on its use in solid tumours is limited.

Using pre-clinical models of disease, our research showed that ATRA shrinks tumours by 40% compared to a placebo treatment. ATRA works to reduce the incidence of tumours through specific molecules – such as nuclear retinoic acid receptors, a type of receptor that controls the presence or absence of certain proteins. More recently, it’s been shown that ATRA suppresses the expression and activation of a protein called PIN1, a master regulator of cancer-causing genes and tumour suppressors in tumour cells. Our team showed that PIN1 is abundant in liver biopsies of patients with bile duct tumours. ATRA works to reduce the abundance of PIN1 in cells and pre-clinical models of bile duct cancer.

For a full coverage of our studies for a general audience, please read more at The Conversation UK 2015 and The Conversation UK 2021

​