Dana-Farber. US: 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.
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.