Scientists have developed a tool which helps them better understand cancer’s survival tactics and could eventually lead to new treatments for dozens of cancer types.
Some cancers are caused by mutations such as faults in the BRCA1/2 genes, which make it harder for the body to repair damaged DNA.
Inhibitor drugs are used to target those tumours by blocking pathways that cancer cells rely on but which in normal cells are not as important.
Discovering new synthetic lethal pairings
However, this approach, called “synthetic lethality”, has so far mainly been successful in patients with BRCA-mutated breast, ovarian, prostate and pancreatic cancers.
Now, a new research paper published in the journal Nature Genetics suggests that many more types of cancer may contain similar pairs of “synthetic-lethal partner genes”, where cancer cells can survive if one process is disrupted but not two.
A team at The Institute of Cancer Research, London, have developed an algorithm called SYLVER (SYnthetic Lethal Vulnerabilities Exhibiting Reciprocation) designed to review swathes of data from more than 9,300 patients in order to identify more pathways that cancer cells with specific gene mutations rely on.
Potential new drug targets
The researchers noticed that although many cancers have mutations in specific genes that normally prevent cancer (called tumour-suppressor genes) they also have higher levels of a different set of genes which must be present for the cancer cells to survive.
The findings reveal that although some gene mutations cause cancer, they also make cancer cells “addicted” to a whole set of new genes.
The study, funded by Cancer Research UK (CRUK), Breast Cancer Now and Walk the Walk, has revealed a list of proteins that could become potential targets for new drugs that would exploit the “addictions” found in cancers.
Dr Syed Haider, Head of the Breast Cancer Data Science Team at The Institute of Cancer Research, London said:
“This research tells us how some cancer cells survive despite having faulty mutations in key genes.
“We’ve learned that when cancers lose a particular tumour-suppressor gene, which usually work to protect our cells from becoming cancerous, they ramp up the activity of back-up processes controlled by other genes to stay alive.
“This is an effect known as buffering. Buffering in cells has been known about for a long time, but our large-scale analysis of over 9,300 patients with different cancers shows that buffering occurs in most cancers and the genes that are increased for the cancer to survive are different, depending upon which tumour suppressor gene is lost. This could mean more potential new treatments for even more types of cancer.”
Professor Chris Lord, Professor of Cancer Genomics and Deputy Director of The Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, said:
“In the short-to medium-term, our findings suggest there might be more precise ways to design cancer drugs for specific cancers. Our immediate plans are to now use these approaches to do just that.
“In the longer term, we hope that using the tools we have developed, we will eventually be able to design drugs that are effective for very specific types of cancer that are difficult to treat. “
Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, said:
“By identifying the genetic alterations that cancer cells rely on to survive, the researchers have discovered hundreds of potential targets for developing new drugs.
“This approach will help researchers develop more ‘synthetic lethal’ treatments, like PARP inhibitors. Drugs like these will treat breast cancer and other cancers in a way that largely leaves a patient’s healthy cells unharmed.
“We look forward to seeing results from future research and further insights into how this breakthrough may lead to new targeted treatments for this devastating disease.”
Dr Hattie Brooks, research information manager at CRUK, said:
“We are living in a golden age of research where we can use patient data in new ways to help us better understand cancer and how to beat it.
“We were pleased to fund this research and look forward to seeing how this work might contribute to the development of new cancer drugs, which may help more people live longer, better lives, free from the fear of cancer.”
The study was supported by The Cancer Genome Atlas (TCGA) Research Network and the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.