Gene changes may be responsible for recurrent HNC

Gene alterations may be responsible for recurrent head and neck cancer (HNC) in some patients, and an existing cancer drug may be an effective treatment, according to research presented at this week's American Association for Cancer Research annual meeting in San Diego.

Researchers who examined the genetic landscape of HNC found that while metastatic and primary tumor cells share similar mutations, recurrent HNC is associated with certain gene alterations that could be vulnerable to an existing cancer drug, according to research from the University of Pittsburgh Cancer Institute (UPCI) and the Yale University School of Medicine.

About half of patients diagnosed with head and neck squamous cell cancers already have disease that has metastasized to the lymph nodes, explained Jennifer Grandis, MD, a professor and the vice chair of research in the department of otolaryngology at the University of Pittsburgh School of Medicine and the director of the Head and Neck Program at UPCI. About 20% to 30% of patients are thought to be cured of the disease, yet go on to develop recurrent cancer. This recurrent cancer typically does not respond to standard treatments.

"We decided to compare the genetic signatures of tumor cells from primary tumors with those from disease that had spread and cancers that were thought cured but then came back in the hopes of getting some clues about how best to guide therapy in these different settings," Dr. Grandis said in a statement. "We found that recurrent cancers might have an Achilles' heel we can exploit to kill them."

The team conducted the first whole-exome genetic sequencing study on what Dr. Grandis called its "treasure trove" of frozen patient samples and found similar mutations both in primary tumors and the lymph nodes to which their cancers had already spread. But there were different mutations in tumors that had recurred after a period of remission that were not found in their original cancers.

"The recurrent tumors carried mutations in a gene area that encodes for DDR2 cell receptors," Dr. Grandis said. "Other studies have shown that DDR2 mutations can confer sensitivity to the cancer drug dasatinib, which could mean that drug has promise in the treatment of recurrent head and neck cancers."

The researchers suggested further investigation of dasatinib treatment.

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