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Targeted therapy uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells. These therapies attack the cancer cells’ inner workings – the programming that makes them different from normal, healthy cells. Each type of targeted therapy works differently, but all change the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

Genetic testing for cancer of unknown primary (CUP) samples

The tumor sample removed from a patient with CUP is typically tested for "targetable mutations." This means that the tumor undergoes genetic testing, also known as next generation sequencing or genomic profiling. The results may show if the tumor has DNA mutations that would respond to current targeted therapy. Examples of tumor mutations which may respond to specific targeted therapy include EGFR, ALK, ROS1, BRAF, NTRK, HER2, KRAS and others.

One target on squamous cell cancers of the head and neck is called epidermal growth factor receptor (EGFR). Cells from many of these cancers have too many copies of EGFR, which helps them grow faster and become more resistant to radiation or chemotherapy (chemo). A drug called cetuximab (Erbitux) blocks EGFR, and can help patients with squamous cell cancers of the head and neck area. It’s often used along with radiation or chemotherapy (chemo), but it can also be used by itself to treat people whose cancers no longer respond to chemo and who can’t take radiation.

Targeted therapy drugs for cancer of unknown primary (CUP)

A number of targeted therapy drugs are used to treat breast cancer, including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), everolimus (Afinitor), ado-trastuzumab emtansine (Kadcyla, also known as TDM-1), and neratinib (Nerlynx). For more information, see Targeted Therapy for Breast Cancer.

Other targeted therapy drugs are used for cancers that start in other areas, and may be helpful in some cases of cancer of unknown primary. For example, sunitinib (Sutent) and everolimus (Afinitor) are helpful in treating pancreatic neuroendocrine cancer, and may be used to treat well-differentiated neuroendocrine cancers of unknown primary.