How sharing cancer data can save lives

Professor Mark Lawler at the Centre for Cancer Research and Cell Biology (CCRCB) at Queen’s University Belfast and lead author of the study said: “Current restrictions on data sharing across borders limit the data that can be used by researchers to carry out a comprehensive analysis of cancer. “This is particularly pertinent when researching rare … Continue reading “How sharing cancer data can save lives”

Professor Mark Lawler at the Centre for Cancer Research and Cell Biology (CCRCB) at Queen’s University Belfast and lead author of the study said: “Current restrictions on data sharing across borders limit the data that can be used by researchers to carry out a comprehensive analysis of cancer.

“This is particularly pertinent when researching rare types of cancer. If data is limited to a particular region or country, low patient numbers can make clinical research impossible. But it can also pose challenges with common cancers such as breast cancer, which is made up of different subtypes. We need as much information as possible to help develop new diagnostic tests and treatments for these different subtypes.”

Charles Sawyers of the Memorial Sloan-Kettering Cancer Center in New York and co-author of the paper said: “If we get this right, we can really use the data to help us in our aspiration to improve outcomes in this deadly disease.”

Taking the lives of over 8.5 million people every year, cancer is a global challenge demanding a global response. The paper, published in the New England Journal of Medicine (NEJM) was conducted by a coalition of world leading cancer experts under The Global Alliance for Genomics and Health and led by Queen’s University Belfast.

World-leading cancer researchers highlight the urgent need to foster a more collaborative culture, to work together and share data for the benefit of cancer patients around the world. Professor Lawler said: “Such an aspiration depends on both effective collaboration as well as dedicated resources. We hope that our call for a ‘global cancer knowledge network’ energises the community to act decisively and provide the resources to embed data sharing for the benefit of cancer patients globally. If we do, then big data really can save lives.

“Our experience shows that patients want to get involved to make a positive difference so we need to help them to do that.”

Recently, a group of patients with a rare gene mutation called ROS 1 that can cause different cancers came together online, frustrated about the lack of progress in the treatment of their disease. The online group involving over 130 individuals from eleven different countries approached a disease foundation and they are now involved in the first steps of developing a clinical trial that targets the particular genomic abnormality that causes their disease.

Professor Lawler added: “We are working with the disease foundation to help make this clinical trial a reality. This exemplifies why accessing data is so vital to enable researchers to carry out their work and ultimately to help patients.”

Margaret Grayson, a breast cancer survivor and Chair of the patient group, the Northern Ireland Cancer Research Consumer Forum explained: “Research is vital to improve the quality of life as well as life expectancy for cancer patients. Many patients will be more than willing to get involved and share their clinical information to bring us one step closer to tackling this global health issue.”

Better understanding of how brain tumors ‘feed’

ACSS2 provides tumors a competitive edge by enhancing their ability to use a cellular salt called acetate as a carbon-based food source rather than the more desirable glucose which is often in short supply in cancer cells. This lifeline allows cancer cells at the core of the tumor to survive and even grow as it battles with nutrient deficiency.

Current therapies and the body’s own immune system are not efficient at stopping this vital nutrient pathway in cancer cells, and little is known about how these life-giving proteins are transported from cytosol, a liquid cell component, into the nucleus via a process called nuclear translocation. The ability to halt nuclear translocation of ACSS2 would cut off the cancer cell’s self-maintaining ability at its most basic level. The study, led by Zhimin Lu, Ph.D., professor of Neuro-Oncology, provided new information about nuclear translocation and how ACSS2 may offer a new approach for therapy.

“Overcoming metabolic stress is a critical step in solid tumor growth. Acetyl coenzyme A (CoA) generated via glucose and acetate uptake is a key carbon source for important cellular processes such as histone acetylation and gene expression,” said Lu. “However, how acetyl CoA is produced under nutritional stress is unclear. Our study explains the underlying mechanics of how this occurs, with ACSS2 as a novel and important method for gene expression under these circumstances.”

Using a CRISPR gene editing process, Lu’s team revealed what roles ACSS2 plays in histone acetylation by generation of nuclear acetyl-CoA from acetate within the cell’s nucleus. It also demonstrated the significance of histone modification via a metabolic enzyme in maintaining cell stability and tumor development. Histones are proteins that act as spools around which DNA winds and are crucial to gene regulation, while histone acetylation is a modification process critical to gene expression.

In essence, ACSS2 gives genetic permission for the production of lysosomes, cellular structures that serve as the cell’s waste disposal system, thus ridding the cell of unwanted materials, while recycling digested products for protein, DNA, and lipid synthesis. Lysosomes are recognized as a contributing factor in tumor development. ACSS2 also promotes a cannibalistic cell-feeding mechanism called autophagy, allowing lysosomes to receive, digest, and recycle much-needed nutrients. When nutrients located outside of the cell are limited, ACSS2 is able to reprogram cancer cell metabolism by increasing autophagy and reusing lysosome-digested products from unwanted or stored materials for cell survival and growth.

“These findings elucidate an instrumental interplay between reprogramming of metabolism and gene expression in cancer cells,” said Lu. “Inhibition of both ACSS2’s nuclear function and the metabolic pathway known as glycolysis, which converts glucose to tumor-feeding energy, appears to be an efficient approach for cancer treatment.”

Designer viruses stimulate the immune system to fight cancer

Most cancer cells only provoke a limited reaction from the immune system — the body’s defense mechanism — and can thus grow without appreciable resistance. By contrast, viral infections cause the body to release alarm signals, stimulating the immune system to use all available means to fight the invader.

Bolstered defenses

Immunotherapies have been successfully used to treat cancer for many years; they “disinhibit” the body’s defense system and so also strengthen its half-hearted fight against cancer cells. Stimulating the immune system to specifically and wholeheartedly combat cancer cells, however, has remained a distant goal. Researchers have now succeeded in manufacturing innovative designer viruses that could do exactly that. Their teams were lead by Professor Doron Merkler from the Department of Pathology and Immunology of the Faculty of Medicine, UNIGE, and Professor Daniel Pinschewer from the Department of Biomedicine, University of Basel.

The researchers built artificial viruses based on lymphocytic choriomeningitis virus (LCMV), which can infect both rodents and humans. Although they were not harmful for mice, they did release the alarm signals typical of viral infections. The virologists also integrated certain proteins into the virus that are otherwise found only in cancer cells. Infection with the designer virus enabled the immune system to recognize these cancer proteins as dangerous.

The unique combination of alarm signals and the cancer cell protein stimulated the immune system to create a powerful army of cytotoxic T-lymphocytes, also known as killer cells, which identified the cancer cells through their protein and successfully destroyed them.

Hope for new cancer treatments

The treatments available to cancer patients have developed enormously in the last few years. However, as the researchers report, current treatments are still inadequate in combating many forms of cancer. “We hope that our new findings and technologies will soon be used in cancer treatments and so help to further increase their success rates,” say the study’s senior authors, Professor Doron Merkler and Professor Daniel Pinschewer. This very promising designer virus has already been patented through Unitec, a structure that offers advice as well as industrial and financial contacts to UNIGE, the University Hospital and the University of Applied Sciences and Arts of Geneva researchers.