An international team of scientists is reporting a significant milestone for cancer research after charting 21 major mutations behind the vast majority of tumors.
The disruptive changes to the genetic code, reported in Nature, accounted for 97% of the 30 most common cancers.
Finding out what causes the mutations could lead to new treatments. Some causes, such as smoking are known, but more than half are still a mystery.
A tumor starts when one of the building blocks of bodies, a cell, goes wrong. Over the course of a lifetime cells pick up an array of mutations which can eventually transform them into deadly tumors which grow uncontrollably.
The international team of researchers was looking for the causes of those mutations as part of the largest-ever analysis of cancer genomes.
Cancer researchers charted 21 major mutations behind the vast majority of tumors
The well-known ones such as UV damage and smoking mutate the DNA, increasing the odds of cancer.
But each also leaves behind a unique hallmark – a piece of “genetic graffiti” – that shows if smoking or UV radiation has mutated the DNA.
Researchers, led by the Wellcome Trust Sanger Institute in the UK, hunted for more examples of “graffiti” in 7,042 samples taken from the 30 most common cancers.
The found that 21 separate “graffiti signatures” could account for 97% of the mutations which led to cancer.
Other signatures were related to ageing and the body’s immune system. Cells respond to viral infection by activating a class of enzymes which mutate the viruses until they can no longer function.
However, 12 of the signatures defy explanation for now.
It is hoped that if some of them can be pinned down to things in the environment then new ways of preventing cancer could be developed.
It may also spur further research. One of the unknown causes of mutation happens only in neuroblastoma, a cancer of nerve cells which normally affects children, so something unique is happening there.
The root genetic cause of leukaemia has been traced back to early life in the womb, scientists say.
Experts from the Institute of Cancer Research in London, UK, analyzed the entire three billion letter sequence of DNA-coding in identical twins to reveal what sets off the disease.
Researchers hope the findings, published in PNAS journal, could lead to new drugs to fight the condition at source.
Leukaemia is the most common cancer diagnosed in children.
The root genetic cause of leukaemia has been traced back to early life in the womb
Researchers studied twins studied that had the most common form of leukaemia that affects children – acute lymphoblastic leukaemia (ALL), which is a cancer of the white blood cells.
It is already known that multiple faulty genes are linked to the condition and that environmental factors probably act as triggers along the way. But the precise sequence of events leading up to a diagnosis of ALL is unclear.
The scientists wanted to find out more about the disease so that, ultimately, a better treatment could be found.
Although ALL is often curable, the medicines used to treat it can cause unpleasant and sometimes severe side effects.
Prof. Mel Greaves and his colleagues decided to study identical twins who shared the same DNA inherited from their parents.
Both twins developed ALL in early childhood, at around four years of age.
By comparing blood and bone marrow samples of the twins in later childhood, the researchers found one genetic mutation identical in both twins – a common leukaemia-causing gene called ETV6-RUNX1.
The scientists reason that this mutation must have arisen in one of the twins while in the womb.
Cells carrying the mutation then spread to the other twin via their shared placental blood circulation.
The identical twins had a total of 22 other mutations, but none of these mutations was shared by both twins, and so they must have accumulated after birth as the disease progressed, say the researchers.
Study co-author Prof. Mel Greaves said: “We were able to sequence the entire human genome. It told us for the first time that this is the key mutation that starts the whole process of leukaemia. The other mutations must have happened after birth.”
British researchers have found that an experimental “Trojan-horse” cancer therapy has completely eliminated prostate cancer in experiments on mice.
The team hid cancer killing viruses inside the immune system in order to sneak them into a tumor.
Once inside, a study in the journal Cancer Research showed, tens of thousands of viruses were released to kill the cancerous cells.
Experts labeled the study “exciting,” but human tests are still needed.
Using viruses to destroy rapidly growing tumors is an emerging field in cancer therapy, however one of the challenges is getting the viruses deep inside the tumor where they can do the damage.
“There’s a problem with getting enough virus into the tumor,” said Prof. Claire Lewis from the University of Sheffield.
She leads a team which uses white blood cells as “Trojan horses” to deliver the viral punch.
British researchers have found that an experimental Trojan-horse cancer therapy has completely eliminated prostate cancer in experiments on mice
After chemotherapy or radiotherapy is used to treat cancer, there is damage to the tissue. This causes a surge in white blood cells, which swamp the area to help repair the damage.
“We’re surfing that wave to get as many white blood cells to deliver tumor-busting viruses into the heart of a tumor,” said Prof. Claire Lewis.
Her team takes blood samples and extract macrophages, a part of the immune system which normally attacks foreign invaders. These are mixed with a virus which, just like HIV, avoids being attacked and instead becomes a passenger in the white blood cell.
In the study, the mice were injected with the white blood cells two days after a course of chemotherapy ended.
At this stage each white blood cell contained just a couple of viruses. However, once the macrophages enter the tumor the virus can replicate. After about 12 hours the white blood cells burst and eject up to 10,000 viruses each – which go on to infect, and kill, the cancerous cells.
At the end of the 40-day study, all the mice who were given the Trojan treatment were still alive and had no signs of tumors.
By comparison, mice given other treatments died and their cancer had spread.
Prof. Claire Lewis said: “It completely eradicates the tumor and stops it growing back.”
She said it was a “ground-breaking” concept, but cautioned that many remarkable advances in treating mice failed to have any effect in people.
Researchers have discovered the cells in tumors that seem to be responsible for their re-growth.
Three separate studies on mice appear to have confirmed the view that the growth of tumors is driven by so-called cancer stem cells.
The researchers claim to have resolved one of the biggest controversies in cancer research and say their work marks a “paradigm shift” in the field.
The studies have been published in the journals, Nature and Science.
Doctors often successfully reduce the size of tumors through various therapies, but often patients suffer a relapse and the tumor re-grows.
Three separate studies on mice appear to have confirmed the view that the growth of tumors is driven by so-called cancer stem cells
Some researchers believe that this happens because therapies fail to eradicate a small proportion of cells that drive tumor growth known as cancer stem cells. They believe that these are the cells that should be targeted to eliminate the tumor forever.
Evidence for the existence of cancer stem cells has been weak. But now three separate groups of researchers working independently have found direct evidence of cancer stem cells driving tumor growth in brain, gut and skin cancers.
The suggestion is that the same may be true of all cancers which produce solid tumors.
According to Prof. Cedric Blanpain of the Free University of Brussels, who led one of the studies, the results could pave the way for a new approach to treating many cancers.
“If these cells are indeed the cells that fuel tumour growth then maybe you can target these cells,” he said.
But that may be easier said than done. The newly-identified cancer stem cells are very similar to healthy stem cells responsible for growing and renewing tissue in the body. Any therapy to target cancer stem cells may also destroy healthy tissues. A priority for researchers will be to see if there are important differences between normal and cancer stem cells so that therapies can distinguish between them.
But according to Prof. Hugo Snippert of the University Medical Centre in Utrecht, who led the study into intestinal tumors, the confirmation that these cells exist is an important step in future cancer research.
“Many argued that these cells did not exist. But we have shown for the first time there is such a thing as a cancer stem cell and that tumors are maintained by them,” he said.
Prof. Luis Parada of the University of Texas, who led research that identified stem cells in brain tumors in mice, said he believed there would now be a new approach to developing new treatments for solid tumor cancers.
“Cancer stem cells change the paradigm. The goal of shrinking tumors may well turn out to be less important than targeting the cancer cells in that tumor.”
British researchers have shown that a tumor-killing virus can sneak around the body by “hitchhiking” on the back of blood cells.
It is hoped reoviruses can be used to treat cancer, but there were fears they would not work if the immune system could wipe them out.
A study published in Science Translational Medicine showed the viruses could hide in the blood and reach their target.
Experts said it was an important step in advancing cancer therapies.
Reoviruses are normally harmless, but they can cause stomach upsets and colds in childhood. However, it seems they have the ability to infect and kill some cancerous cells while leaving the surrounding tissue unharmed.
However, experiments on mice suggested the virus would not survive in the blood as the immune system would destroy it.
It meant the virus would need to be injected directly into the tumour or be given with drugs to suppress the immune system.
British researchers have shown that a tumor-killing virus can sneak around the body by "hitchhiking" on the back of blood cells
A study in 10 people at the University of Leeds and The Institute of Cancer Research, at the Royal Marsden Hospital, showed that the virus could escape the immune system by hiding in the blood.
All the patients had advanced bowel cancer which had spread to the liver, and were injected with doses of the reovirus ahead of their scheduled surgery.
The virus was detected in the tumor, but not the liver, meaning it was selectively targeting the cancer. In the blood, the virus was detected in blood cells, not the liquid blood plasma all the cells float in, meaning it was “hitchhiking”, the researchers said.
Prof. Alan Melcher, from the University of Leeds, said the virus was “even cleverer” than previously thought.
“By piggybacking on blood cells, the virus is managing to hide from the body’s natural immune response and reach its target intact.”
Prof. Alan Melcher said he had “no doubt” the virus would be eventually used “in combination with chemotherapy”.
Dr. Kevin Harrington, from the Institute of Cancer Research, said: “Viral treatments like reovirus are showing real promise in patient trials.
“This study gives us the very good news that it should be possible to deliver these treatments with a simple injection into the bloodstream.”
Why reoviruses affect only cancer cells is not entirely understood. Cancer cells behave very differently to healthy cells, which may make them more susceptible to infection.
Doctors are already testing the virus in some trials in people, such as studies on head and neck cancer.
Prof. John Bell, from the University of Ottawa, has researched using genetically modified viruses to attack cancer cells.
He said viruses could be “exquisitely selective” in targeting tumors, and that this latest study had shown how safe the technique was.
“This study is an important next step in advancing oncolytic virus therapies into cancer patients.”
Experts say a genetic test could help predict breast cancer many years before the disease is diagnosed.
Ultimately the findings, in the journal Cancer Research, could lead to a simple blood test to screen women, they say.
The test looks for how genes are altered by environmental factors like alcohol and hormones – a process known as epigenetics.
One in five women is thought to have such a genetic “switch” that doubles breast cancer risk.
The scientists from Imperial College London analyzed blood samples from 1,380 women of various ages, 640 of whom went on to develop breast cancer.
And they found a strong link between breast cancer risk and molecular modification of a single gene called ATM, which is found on white blood cells.
A genetic test could help predict breast cancer many years before the disease is diagnosed
They then looked for evidence of what was causing this change. Specifically, they looked for a chemical effect called methylation, which is known to act as a “gene switch”.
Women showing the highest methylation levels affecting the ATM gene were twice as likely to develop breast cancer compared with those with the lowest levels.
In some cases the changes were evident up to 11 years before a breast tumor was diagnosed.
Dr. James Flanagan, of Imperial College London, who led the new research, said: “We know that genetic variation contributes to a person’s risk of disease.
“With this new study we can now also say that epigenetic variation, or differences in how genes are modified, also has a role.
“We hope that this research is just the beginning of our understanding about the epigenetic component of breast cancer risk and in the coming years we hope to find many more examples of genes that contribute to a person’s risk.
“The challenge will be how to incorporate all of this new information into the computer models that are currently used for individual risk prediction.”
It is not yet clear why breast cancer risk might be linked to changes in a white blood cell gene.
But the team envisages that a blood test could be used in combination with other information about breast cancer risk, such as family history and the presence of other known breast cancer genes, to help identify those women at greatest risk of developing the disease in the future.
These women could then be closely monitored and offered pre-emptive treatment, such as surgery.
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