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Probing a group of proteins to develop novel ways to detect and treat cancer

The cells in our body produce a group of proteins called Kallikrein-related peptidases, or KLKs for short. It’s known that these proteins play an important role in a variety of biological processes involved in the development and progression of cancer, but researchers currently lack the technology to study KLKs accurately in cancer cells.

Professor Edward Tate, based at Imperial College London, is a chemical biologist who through his career has developed techniques to produce chemical probes to study the activity of proteins within cells. These probes allow scientists to measure how active specific proteins are in cancer cells and use this information to develop new ways to diagnose and treat cancer.

Professor Tate is now developing probes to study the activity of KLKs in prostate, ovarian and pancreatic cancer cells. His team will use their results to identify chemicals that can block KLKs in these cells with the goal to open up new avenues for cancer treatment. They will also test the probes in biological samples from cancer patients to understand if measuring KLKs could be used as a way to more accurately diagnose patients.

The importance of fat in the aggressiveness of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. Unfortunately, due to a lack of therapies, late detection and its aggressive nature, most patients do not survive the first twelve months after diagnosis.

Dr Patricia Sancho and her team at the Instituto de Investigación Sanitaria Aragón in Zaragoza, Spain, are trying to uncover the biological mechanisms that make PDAC such an aggressive cancer. Cancer stem cells – cells that can generate new tumours - are essential for the growth and spread of pancreatic cancer. Cancer stem cells can obtain their energy from a wide range of biological molecules, including fats. Because they are able to store fat for later use, cancer stem cells can thrive in nutrient-sparse conditions, such as the immediate tumour environment.

Dr Sancho and her team are now investigating how the ability of cancer stem cells to store and use fat as an energy source enables them to spread throughout the body. In particular, they want to find out how cancer stem cells break free from the original tumour and spread through the blood stream to other parts of the body when nutrients in the original tumour become sparse. Understanding how cancer cells use fat to survive, thrive and spread is an essential step towards identifying new potential drug targets that could be used to develop much needed therapies for this very aggressive form of cancer.

Cutting communication between normal and tumour cells in pancreatic cancer

Dr Angus Cameron and his team at Barts Cancer Institute, Queen Mary University, London, are using funding from Worldwide Cancer Research and Pancreatic Cancer Research Fund to find out how normal cells in pancreatic tumours are recruited by cancer cells to support the growth and progression of the disease.

Tumours aren’t just masses of cancer cells but also contain lots of normal cells that have been recruited by the tumour to help it grow. One of these cells is known as a cancer-associated fibroblast (CAF) and evidence shows that they play a critical role in the progression of cancer. They have a strong presence in pancreatic cancer and Dr Cameron’s team have recently identified a new protein, which is required for CAFs to assist the growth of a tumour.

The team have developed a genetically engineered mouse which they now want to use to study exactly how this protein allows CAFs to communicate with tumour cells and whether there is an effective way to block this communication so that tumour growth can be prevented. This will not only give a better understanding of the biology of pancreatic cancer but could also identify a new drug target for treating one of the deadliest cancers.

Worldwide Cancer Research findings presented to House of Commons

A PhD student funded by Worldwide Cancer Research at the University of Hertfordshire has this week displayed her research at the House of Commons.

Deborah Ogbeni was selected along with 175 other finalists from over 500 entries across the country to share her research into identifying a potential new treatment for pancreatic cancer. The event was organised by STEM as part of British Science Week.

Her work, an extension of a project initiated by Dr Stewart Kirton and Dr Sharon Rossiter at the University of Hertfordshire and Dr Tatjana Crnogorac-Jurcevic at Queen Mary University London, was funded by the charity Worldwide Cancer Research to investigate treatments for this form of cancer.

Deborah’s research has identified lead compounds that could be developed as a suitable drug to prevent the spread of cancer. Further research is needed, but the drug has the potential to both slow down the progression of pancreatic cancer and make it more vulnerable to chemotherapy.

Deborah said:

“It was an honour to be able to showcase my research at such a prestigious event. I am excited to think that this research could one day improve the treatment potential and life chances of people with pancreatic cancer.”

STEM for Britain is a national competition which aims to raise the profile of Britain's early-stage researchers at Westminster by engaging Members of both Houses of Parliament with current science, engineering and mathematics research being undertaken in the UK. Deborah’s research was part of the Biological and Biomedical Science session and MPs attended to view the range of ground breaking research being carried out in their constituencies.   

Dr Lara Bennett, Science Communications Manager at Worldwide Cancer Research, commented “It is great that Deborah’s project was so successful in identifying potential new cancer drugs for pancreatic cancer. The survival rate for this type of cancer is still extremely low and has not improved much since the 1970s so new treatments are urgently needed. It is a great achievement for Deborah to present her findings in parliament and an experience I am sure she will always remember.”

Boosting immunotherapy treatments to treat pancreatic cancer

Dr Li Wang in the US is developing a new type of ‘cancer vaccine’ immunotherapy treatment for pancreatic cancer.

Pancreatic cancer is often resistant to standard radiation and chemotherapy, and is still very hard to treat in many patients. Immunotherapy treatments, which involve training the body’s own immune system to fight against cancer are already doing well in a number of cancer clinical trials, but not yet against pancreatic cancer.

Dr Wang and her team think they might have found a way to enhance one particular type of upcoming cancer vaccine immunotherapy, to make it effective against pancreatic cancer.

“Antibodies which block a set of cell proteins called immune checkpoint proteins have become the breakthrough therapies for late-stage melanoma patients,” says Dr Wang. “However, the same treatment has so far failed to bring survival benefits for pancreatic cancer patients.”

“In my lab we have recently identified a type of immune checkpoint protein which early tests suggest might be linked to pancreatic tumour growth. We now want to investigate further whether blocking this new protein will help enhance the effectiveness of the cancer vaccine immunotherapy treatment against pancreatic cancer.”

In this project the researchers will carry out a number of tests in the lab to understand exactly how this method works against tumours, and find out how effective blocking the new protein might be.

“Ultimately we hope this new work will help us begin to formulate and test a brand new therapy for patients with pancreatic cancer,” says Dr Wang.

Testing a dual combination therapy for pancreatic cancer

Pancreatic cancer is a devastating disease. Less than 1% of people diagnosed survive for more than ten years, which is the same as it was back in the 1970s. Professor Hodivala-Dilke explains “Where surgery is not a possibility, chemotherapy is given, but often, toxic side effects mean that treatment has to be stopped. Pancreatic cancer has several specific features that make it particularly difficult to treat. These include the fact that they have a poor blood supply, which means that the much of the chemotherapy that we treat the tumour with never even reaches it. In addition, pancreatic cancers can have complex genetic mutations that can alter therapy responses.

To overcome this, with the help of a previous Worldwide Cancer Research grant, we have developed a dual action treatment strategy. It can improve the delivery of Gemcitabine (a chemotherapy often given to patients) to pancreatic cancer with mutations in a subset of genes. It also helps the Gemcitabine work more effectively in the cancer cells so that we can reduce its dose and therefore reduce side effects, whilst still improving survival. With this latest grant we are aiming to extend these studies to pancreatic cancer with other genetic mutations and investigate whether this strategy can improve the effect of other commonly used chemotherapies.

Our data will provide new information that will help us to treat pancreatic cancer better, hopefully in the not too distant future.”

New year, new research

We support research into all cancer types and this latest grant round was no exception. The projects contain a good mix of cancer types from mouth and lip to breast, lung, pancreatic, lymphoma and liver cancer to name but a few. And of course a large amount is being spent on understanding the very fundamental principles behind how our cells behave and what goes wrong in cancer. Keeping with our ethos of supporting the best research around the globe, the projects are taking place all over the world including England, Portugal, Greece, Spain, Australia, The Netherlands, France, Germany, USA and Canada.

Opening up about mouth cancer

Some of the projects that most excite us are Dr Guy Lyons from the University of Sydney, Australia. He is identifying genetic changes that occur when mouth cancer starts so that it can be diagnosed early, when treatment is more likely to be successful. You can read more about mouth cancer in our recent blog. Dr Lyons told us “The support of organisations such as Worldwide Cancer Research for research into the fundamental biology of cancer is essential for the discovery of new paradigms that enable new approaches in the clinic down the track.”

Developing new ‘super cameras’

Professor Carolyn Moores at Birkbeck University of London in England is developing state of the art electron microscopy to actually visualise where drugs bind (stick) to their target molecules inside the cancer cells. This is VERY cool.  She said “Revolutionary new imaging technology means that our pictures will provide unprecedented detail, from which we will calculate the three-dimensional shape of our samples. This technique could potentially revolutionise the way drug discovery is carried out and our findings could be used to design specific drugs that can be further developed to improve treatments for cancers in the future. It is an exciting time to be an electron microscopist and we are thrilled that Worldwide Cancer Research is supporting our research in this area.”

Studying ‘bubbles’ to beating childhood brain cancer

We are also funding Dr Kasper Rouschop at Maastricht University in The Netherlands (pictured above) who is studying how ‘bubbles’ released by glioblastoma tumours encourage blood vessels to grow into the tumour. Glioblastoma’s are a type of brain tumour that commonly effects.  He told us “We anticipate that the results of this research will enable us to evaluate whether targeting these particular bubbles could be a potential new way to reduce the growth of brain tumours.  Our approach is highly innovative and is based on our previous identification of “bubbles” that are specifically released by hypoxic tumour cells. Without the support of Worldwide Cancer Research, evaluation of this promising approach would not be possible.”

And last, but by no means marking the end of my list of fab new projects, is Dr Ruben van Boxtel at the Hubrecht Institute in the Netherlands. He is trying to figure out why cancer arises in some parts of the body more than others. Great question to try to answer!

Our next grant round is already underway and our Scientific Committee will meet in March to decide who gets funded.  But this relies on donations, no money means no research.  If you would like to join team Worldwide Cancer Research and make a donation today just text WORLDWIDE to 70004 to donate £10. Thank you.

Image kindly provided by Dr Kasper Rouchop.

STEM Women in Science Day

Today, 11th February 2016, has been declared the inaugural International Day for Women and Girls in Science.  A day we are embracing here at Worldwide Cancer Research as we are funding almost 50 outstanding female researchers all over the world.

These include Professor Kairbaan (Kebs) Hodivala-Dilke at Barts Cancer Institute in London, England (pictured above) who has just started her grant, testing a dual combination therapy for pancreatic cancer, which she developed with a previous grant from us.  She explains “This dual approach can improve the delivery of Gemcitabine (a chemotherapy often given to patients) to pancreatic cancer with mutations in a subset of genes.  It also helps the Gemcitabine work more effectively in the cancer cells so that we can reduce its dose and therefore reduce side effects, whilst still improving survival.  I want to extend these studies to pancreatic cancer with other genetic mutations and investigate whether this strategy can improve the effect of other commonly used chemotherapies.  I have high hopes that our data will provide new information that will help us to treat pancreatic cancer better, hopefully in the not too distant future.”

We are also funding Dr Kate Sutherland at the Walter and Eliza Hall Institute of Medical Research, Australia who is trying to identify what drives lung squamous cell carcinoma. And Dr Eunhee Kim at Memorial Sloan-Kettering Cancer Centre in New York, USA is studying genetic changes in leukaemia.  Dr Kim told us “To me, this project is really exciting because uncovering how certain mutations drive cancer may give rise to opportunities for a new therapeutic approach for leukaemia.”

We are pleased to be funding so many women in science and hope that today raises the awareness that is needed to ensure the next generation of scientists contains even more women.

Designing a new drug against pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that very few people survive from. No effective treatment has been found to treat people with this disease. A protein, called the calcium binding protein S100P, is involved in the growth, survival, movement, and invasion of cells into other tissues. Large amounts of this protein can be found in PDAC, and are also associated with low survival numbers in several other cancers. It may be possible to develop a treatment against PDAC by using S100P.

Dr Rossiter and her team will use their Worldwide Cancer Research grant to find new chemotherapy drugs for pancreatic cancer, which are specifically aimed at attaching to and stopping S100P. This research will combine computer based drug design to better understand the different molecules that drug compounds could potentially attach themselves to, as well as established tests with cancer cells that have the S100P protein. They expect that this will identify the best possible drug compounds for later testing in animal models, which can hopefully be developed into suitable chemotherapy treatments for patients with pancreatic cancer.

Investigating the role of the immune system and inflammation in pancreatic cancer

Worldwide, around 279,000 people were diagnosed with pancreatic cancer in 2008. Sadly this type of cancer has a poor prognosis. By the time someone has symptoms, goes to their doctor and is diagnosed, the disease is very often quite advanced. Dr Maria Pia Protti is using her Worldwide Cancer Research grant to investigate whether the immune system has a role in inducing or increasing inflammation in pancreatic cancer. To carry out this work she will be using human samples from pancreatic cancer patients.