Aug. 08--A new study, conducted by researchers at the Buck Institute for Research on Aging in Novato along with scientists at other institutions across the country, may pave the way for more effective, personalized therapies for cancer.
The study, published in the online edition of the research journal Cell, found that the standard method for classifying cancer tumors, by their tissue of origin, is inadequate.
Dr. Peter Eisenberg, Marin Cancer Care's medical director of research, said the findings are potentially "paradigm changing." "It is very, very exciting," Eisenberg said.
The study performed a molecular analysis of 12 different tumor types and "generally came up with three to five subtypes for each of the cancers, whether it was lung cancer, colon cancer, head-neck cancer, breast cancer, or brain cancer," said Christopher Benz, a principal investigator at the Buck Institute who contributed to the study.
For example, instead of there being just one type of bladder cancer, the study found three, unique subtypes.
In some cases, cancer subtypes from different tissues of origin bore a closer resemblance to each other than to subtypes from the same tissue of origin. One subtype of bladder cancer was virtually indistinguishable from a type of lung cancer while another bladder cancer subtype was most similar to squamous cell cancers arising from the head, neck and lungs.
The study also discovered that basal-like breast cancers, a particularly aggressive class of breast cancer more common in black and younger women, are so molecularly unique they should constitute their own cancer class.
"Even though these basal-like cancers arise in the breast, on the molecular level they have more in common with ovarian cancers and cancers of squamous cell origin than to other subtypes of breast cancer," said Christina Yau, a Buck Institute senior staff scientist who worked on the study, in a prepared release.
The study found that cancers are more likely to be molecularly and genetically similar if they come from the same type of cell, rather than the same type of tissue. Benz said this suggests that the one-size-fits-all approach to treating cancers with the same tissue of origin may be misguided.
Benz said this phenomenon is probably a major reason why some cancer patients respond well to the preferred treatment for stomach cancer, bladder cancer and lung cancer, while others do very poorly.
"A significant fraction of bladder cancers look more like certain lung cancers and therefore should probably best be treated by lung cancer therapies, not just the all-in-one sort of bladder therapy," Benz said.
The study used data from 3,500 different tumors, each of which came from one of 12 different tissue types.
"When we do the molecular classification and have it tell us, as if we're blindfolded as to where these tumors really come from," Benz said, "we come up with not 12 classes but 11 classes, five of which match pretty well with the tissue of origin."
These five were leukemia and ovarian, endometrial, kidney and brain cancer.
"But the other seven types broke into subsets that didn't map 100 percent onto where they came from," Benz said.
Some of these seven were similar enough to be lumped together.
"There are certain lung cancers, head and neck cancers, and bladder cancers that all went into one new class of cancer that we call the squamous-like cancers," Benz said. "That was an example of the convergence of three completely different kinds of cancer."
Other cancers, such as the previously mentioned basal-like breast cancer and bladder cancer, evidenced divergence. They produced one or more new, unique subtypes.
The study concludes that 10 percent of the 3,500 tumors analyzed in the study should be reclassified to provide "a significant increase in the accuracy for the prediction of clinical outcomes."
Benz said, "That is a minimum estimate."
He said that is because the 10 percent figure derives from the distribution of the 12 cancer types among the 3,500 tumors that the study examined.
"We only had about 120 bladder cancers whereas we had over 800 breast cancers to look at. If we had 800 bladder cancer cases, a lot more cancers would have needed to be reclassified," Benz said. "Because it was cancers like bladder cancer that really jumped around the board."
While the new study suggests some cancer patients may be receiving treatments that will prove ineffective, implementing a more targeted approach won't be easy, or cheap.
Benz said using the methods employed by the study it would cost $50,000 to $100,000 just to accurately classify a single tumor's subtype.
"Now is there a simpler way to actually come to that same classification. We think there probably is," Benz said. "But that is work that has to be done."
Eisenberg said another hurdle will be developing effective treatments for new cancer subtypes.
Eisenberg said, "Though we can find the abnormalities in these cancer cells, we don't always have a weapon to target that abnormality."
Eisenberg, however, added, "This study shows the importance of basic science because clearly we don't know enough about how cancer works. Only when we understand the basic mechanisms of the disease, which we will only get from these kinds of studies, will we be able to cure it."
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