Image: Cancerous cells. Courtesy of: National Institute for Allergy and Infectious Diseases
‘Liquid biopsies’ predict cancer evolution
Computer modelling of tumour DNA from a series of blood samples can track the evolution and growth of bowel cancer cells.
If a cancer cell mutates they can evolve to become resistant to treatment, allowing the cancer to return.
Using mathematical modelling, researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust proved it was possible to predict when a cancer would become resistant to a treatment before CT scans were needed.
Study co-leader Dr Andrea Sottoriva, Team Leader in Evolutionary Genomics and Modelling at the ICR, said:
“Our computer model used information from liquid biopsies to predict how a tumour’s genetic make-up would evolve, and estimate how long it would take for the cancer to return – in much the same way that computer models can forecast the weather.”
Ground-breaking study of protein networks in bowel cancer cells
A blind spot in cancer research has been the study of the protein building blocks, known as the proteome, that make up cancer cells.
Scientists have traditionally focused on the all of the genes (known as the genome) and all of the RNA (known as the transcriptome) in cancer.
But in an August 2017 paper, a team of cancer researchers described a detailed study of many of the proteins in bowel cancer cells and how common mutations in cancer affect them. They then investigated whether proteins could play a role in predicting the effect of cancer treatment.
The team tested 265 existing anti-cancer drugs on 50 bowel cancer cell lines, analysing 9,000 proteins. They found they could predict drug responses this way, which were not explained by either genomics or transcriptomics. They therefore suggest future bowel cancer patients should have their proteome, as well as their genome and transcriptome, tested to predict which treatments will work for them.
Dr Jyoti Choudhary, lead author from the ICR, and previously the Wellcome Trust Sanger Institute, said:
“This study is the first detailed characterisation of colorectal cancer cell lines. It is important to include the proteome in cancer research because proteins are the building blocks of life, and networks of proteins working together are known to drive fundamental processes in cancer.”
Combating drug-resistance in bowel cancer
In late 2018, researchers at the ICR found a potential way to re-sensitise bowel cancers that have become resistant to treatment using drugs that reduce inflammation.
The research also showed a potential reason for why a drug, called trametinib, did not do as well as expected in clinical trials as a treatment for bowel cancer.
Dr Steven Whittaker, leader of the Molecular Drug Resistance Team at the ICR, led the research. He said:
“Our research suggests that by suppressing inflammation, it is possible to overcome resistance to drugs like trametinib, potentially opening up new avenues to treating this disease.”
Custom ‘mini-tumours’ may be the future for treatment plans
‘Mini tumours’ grown from biopsy samples achieved success rates of over 88% in predicting if a treatment would work, according to a February 2018 study.
The ‘mini-tumours’ were allowed to grow free form in gel and grew to be almost identical to the original tissue sample sharing 96% of 151 cancer-related genes.
The researchers believe each patient could have their own mini tumours grown and then tested to see how sensitive they are to different drugs and to develop a personalised plan, before their treatment starts.
Study leader Dr Nicola Valeri, Team Leader in Gastrointestinal Cancer Biology and Genomics at the ICR, and a Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“We were able to look in incredible detail at how tumours responded to drugs – including patterns of gene activity and mutation, and even how the cancer would evolve in response to treatment.”
Cara Hoofe, from London, who is currently living with bowel cancer, said:
“With a lot of advanced cancers time is of the essence, the faster you find a treatment that works for you the better.”
Triple drug attack could overcome bowel cancer resistance
Relapse rates due to bowel cancer cells evolving resistances to drug therapies is a common challenge facing clinicians and patients.
Last month, researchers found that by combining a third drug, navitoclax, with two already used drug therapies the emergence of resistance was completely blocked in laboratory tests.
This approach for combining targeted treatments, which can utilise multiple pathways of attack, could have a huge potential for cancer treatment, as it has previously with treatments for HIV and tuberculosis.
Study author Dr Paul Clarke, Senior Researcher in Signal Transduction and Molecular Pharmacology at the ICR, said:
“The research is still at a fairly early stage, but in principle combinations of targeted drugs could be similarly effective against many other cancer types.”
Hidden gene mutations in DNA revealed
A brand new method for unearthing DNA mutations called chromosome conformation capture has been developed at the ICR and, in September 2018, researchers showed how it revealed a new genetic mutation that drives bowel cancer.
The mutations which drive bowel cancer were identified through the spatial orientation of the DNA by looking at its 3D shape when wrapped up in chromosomes.
Mutated genes which caused higher activities of the gene ETV1 could be driving bowel tumour growth.
Professor Richard Houlston, Professor of Population and Molecular Genetics at the ICR said:
“Our team have started to look beyond genes, at the other DNA in cells that can interact with genes and affect how they operate.”
“We have used the technique to identify a new driver of bowel cancer, but it could be employed to study any cancer type. We hope that as well as increasing our understanding of the development of cancer.”
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