image: This is Robert Haddad, MD, leader of the Head and Neck Oncology Treatment Center at Dana-Farber. view more
Credit: Sam Ogden, Dana-Farber
BOSTON - Scientists have published the first comprehensive catalog of genetic mutations and other abnormal changes found in 279 cancers of the head and neck, and have identified several broken molecular pathways that might be targeted by existing and future cancer drugs.
The authors, who include investigators from Dana-Farber Cancer Institute, said the findings should help in developing targeted therapies and bringing the methods of precision cancer medicine to these cancers, which impact about 600,000 patients a year worldwide. The report is being published in the journal Nature.
Head and neck cancers are the latest type of cancer to be profiled by scientists in The Cancer Genome Atlas (TGCA) Network, a federally funded collaboration. The genome atlas project's goal is to study more than 10,000 human tumors at the molecular level to understand the biological causes of cancer and discover new targets for precision drug therapies.
"This is the most comprehensive data set out there, and will lead to hundreds of additional papers and studies using this data set," said Peter Hammerman, MD, PhD, a medical oncologist at Dana-Farber who studies lung and head and neck cancers.
Hammerman led the team that analyzed the results of the research carried out on each of the 279 tumor specimens to look for altered genes, gains or losses of parts of chromosomes, variations in the numbers of copies of genes present in the tumor DNA, and other changes making up the "genomic landscape" of the head and neck cancers.
Robert Haddad, MD, leader of the Head and Neck Oncology Treatment Center at Dana-Farber and an author of the new report, said that the TGCA study "has identified specific genetic alterations not known in the past, and this will help us develop novel therapies."
Hammerman noted that, overall, the analysis of head and neck tumors showed that "the wiring of these cancers is complex, with a lot of heterogeneity from patient to patient, and combinations of targeted drugs may be needed to treat them successfully."
Traditionally, most cancers of the head and neck have been linked to longtime heavy drinking and smoking. But increasingly, these cancers are being diagnosed in people who are infected with the human papilloma virus (HPV); these patients tend to have better outcomes and have different characteristics than those caused by alcohol and tobacco.
The new study found that tumors from HPV-infected patients were different in numerous ways from those related to smoking and drinking, with different broken cellular pathways and gene alterations.
"They seem to be less genomically complex," said Hammerman.
Haddad said the results "confirm the hypothesis that the HPV-positive and HPV-negative are distinct groups of patients." Tumor in HPV-positive patients was found to often have abnormal activity in a growth-signaling pathway, PI3K that is abnormal in many kinds of cancers and can be blocked by drugs currently available and in development. "This is an important finding," he noted.
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This study was supported by National Institutes of Health (NIH) grants: P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025 and RO1 CA 095419.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute, a principal teaching affiliate of Harvard Medical School, is world renowned for its leadership in adult and pediatric cancer treatment and research. Designated as a comprehensive cancer center by the National Cancer Institute (NCI), it is one of the largest recipients among independent hospitals of NCI and National Institutes of Health grant funding. For more information, go to http://www.dana-farber.org.
Journal
Nature