Houston: Genetic vulnerabilities could lead to powerful new treatments for colon cancer and the researchers hope that the drugs designed to strike these weak spots will eventually stop the disease that is almost inevitably fatal once it spreads, a study by an Indian-American professor says.
Scientists increasingly see cancer as a genetic disease defined not so much by where it starts -colon, liver, brain, breast- but by genetic aberrations that are its Achilles' heel.
And with a detailed understanding of which genetic changes make a cancer grow and thrive, they say they can figure out how best to mount an attack.
They caution most of the drugs needed to target the colon cancer mutations haven't been developed.
Indian-American Harvard professor and the principal investigator for the colon cancer study, Raju Kucherlapati, who has been working on this subject for over 20 years, says: "There are significant findings from this study that better inform us about the cancer, and also provides potential new opportunity for treating this cancer."
"In the United States alone, about 150,000 new patients are diagnosed annually with colon cancer, and 50,000 succumb to the disease. Worldwide, colon cancer afflicts half a million people, men and women", he said.
Currently, the treatments for colon cancer are primarily surgery, chemotherapy, and radiation, which Kucherlapati said are "not tremendously effective".
"New ideas and new approaches for therapy for this cancer are needed," he stated, and the latest study, part of the multi-million dollar Cancer Genome Atlas project, brings about just that.
The study was in part remarkable because of its size: with 250 tumour samples tested, it is "the largest conducted by any group."
One of the main findings may allow for targeted therapies. "We found varieties of different types of genetic changes, and each of those changes point out to possibly a different type of approach that you could take," Kucherlapati explained.
Kucherlapati is the Paul C Cabot Professor in the Harvard Medical School Department of Genetics.
His research focuses on gene mapping, gene modification, and cloning disease genes.
For example, the study found that 100 per cent of the cancerous tumors deregulated a particular pathway in the normal cycle of cell division, and 95 per cent of them deregulated another pathway.
The implication is that drugs could target these pathways to stop the cancer.
Another important finding was the basis for high mutation frequencies in certain tumours; about 15 per cent of the tumours in the sample accounted for these.
"We show that different sets of genes were mutated in those tumours, and that's an important observation because it turns out those tumours...respond differently to certain chemotherapeutical agents and the patients who have those tumours have different outcomes than the rest of them," he said.
The researchers also found similarities in the genetic makeup of different types of cancer.
"Today, rectal cancer is treated somewhat differently than colon cancer," Kucherlapati pointed out, but the study found that the two cancers are actually very similar to each other. Furthermore, drugs that have been used for breast cancer may be effective in 5 per cent of colon cancer patients, too, due to a genetic similarity.
"It might take a few years for some of these therapies to become common place but this sort of opens the door and is a great opportunity to change the therapeutic agents for this cancer."
However, researchers caution that, although much is known about genetic changes that occur in colon cancer, treatment has not caught up.
"It is going to take time, and it is going to take effort," said Charles Fuchs, a Harvard gastrointestinal cancer expert who was an author of the study.
Still, he added, "I don't want to minimise the singular importance of this paper. It is transformative."
Researchers have studied colon cancer before and have identified mutations that seemed critical, but their work lacked the new project's scope and provided more limited data on genetic changes, said Sanford Markowitz, a Case Western Reserve University expert on colon cancer genomics, who is also an author of the new study. |
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