Scientists at Washington University in St. Louis reached a new milestone in cancer research this month with the completion of a comprehensive analysis of the molecular underpinnings of the causes of the disease.
The National Institutes of Health funded the PanCancer Atlas project, more than a decade in the making. Biologists from more than two dozen institutions analyzed DNA from 11,000 cancer patients with 33 major types of the disease, including breast and pancreatic cancer.
The analysis is part of a larger NIH initiative called the Cancer Genome Atlas.
All cancer results from a glitch in DNA. When a gene mutates, the body starts producing abnormal growths of cells. By studying the DNA sequences of cancer cells, scientists say they can better understand what causes tumors to develop and how they spread.
The atlas “allows us to not only look at individual cancer patients and individual cancer types, but also to look at all 33 cancer types together to investigate their relationships, differences and commonalities, “ said Li Ding, director of computational biology at Washington University and lead scientist of the project.
Doctors and patients have traditionally viewed cancer as a disease of organs, said Ding, lead author of one of the project’s three flagship papers. Thanks to molecular sequencing, scientists are beginning to realize that cancer can also be seen as a disease of genes.
Ding and her colleagues studied how certain mutations that occur in a person’s original DNA over time are related to how cancer progresses. For example. the BRCA1 gene, has long been associated with certain types of cancer. (Actress Angelina Joliefamously underwent a mastectomy after learning she carried a BRCA1 mutation, and as a result, it’s known as the “Angelina Jolie Gene.”)
Ding and her colleagues’ research clarified what BRCA1 mutations caused tumor growth and which were harmless. It also found the gene was associated not only with breast and ovarian cancer, but with cervical and colorectal cancer.
In all, the scientists found that out of the 11,000 mutations studied, 8 percent were likely to result in a risk of cancer.
Now that scientists know what mutations drive tumor development, “we can specifically target those changes that are driving the initiation and progression of cancer,” Ding said.
Another PanCancer Atlas study found certain types of tumors arise in particular cell types. Determining how those genes are expressed could lead to more tailored treatments for cancer patients, says NIH Director Francis Collins.
Understanding the molecular basis of cancer is at the heart of the emerging field of precision medicine: treatment that targets individual patients’ DNA.
However, some scientists say large databases often don’t result in better treatment. And even in the cancers that do respond to targeted treatment, relapses still happen.
“You can depict me as a wet blanket,” said Robert Weinberg, a leading expert in cancer genetics and a founding member of the Massachusetts Institute of Technology’s Whitehead Institute, “[but] more often than not, these kinds of datasets don’t afford someone a linear and unambiguous ability to predict the future behavior of a tumor, or of a patient or a different kind of therapy.”
It’s possible the PanCancer gene library could be more “interpretable” and useful to doctors five years from now, Weinberg said, but there’s a chance it might end up “languishing in a databank.”
“There’s been a great love affair of generating these large datasets with no clear vision always as to what conclusions they would lead to and how they will actually be useful,” he said.
Ding and Weinberg do agree on at least one point: Both say for now, targeted molecular therapies are a way to complement more traditional cancer treatments, such as chemotherapy.
The Cancer Atlas results appear in 27 papers across different publications of Cell journals.
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