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Research into the causes, diagnosis, and treatment of cancer is being done at many cancer research centers. Scientists are making progress in understanding how changes in a person’s DNA can cause normal cells to develop into cancer. A greater understanding of the gene and molecular changes that can occur in cancer is providing insight into why these cells become abnormal. Some of these advances may lead to better diagnosis and treatment of cancer of unknown primary (CUP).

Research into the diagnosis of cancers of unknown primary

It’s important for doctors to be able to identify where cancers of unknown primary start so that the most effective treatments can be used. Recent biological and technological advances have made diagnostic options for CUP more effective, including:

Molecular cancer classifier assays (MCCAs)

These assays, or tests, are also known as gene expression profile assays. MCCAs help predict what type of tumor, or subtype of tumor, was biopsied. These assays, or tests, help predict what type of tumor, or subtype of tumor, was biopsied. An MCCA compares genes that are expressed, or turned on, in the biopsied tumor with a database of genes that have been shown to be turned on in specific tumor types. A match using this method accurately predicts the tissue of origin, even if the anatomic primary site cannot be found.

Immunohistochemical (IHC) staining

Recent advances have made IHC staining an essential test for identifying many types of cancer. IHC looks for certain proteins in a tumor that are hallmarks of specific types of cancer. Combining the results of MCCA and IHC tests can be even more helpful in narrowing down the site of origin of a CUP.

Comprehensive Molecular Profiling (CMP)

CMP looks for a broad group of genes in a biopsy sample to find potential genetic alterations. These include genes most commonly associated with breast cancer (BRCA and HER2), lung cancer (ALK), and others such as EGFR, BRAF, TRK, RET, ROS1, and FGFR. CMP is usually done on tissue biopsies, but blood-based liquid biopsies (circulating tumor DNA) is also possible. When these molecular alterations are found, they can guide treatment decisions and help select targeted therapies that may effectively treat the cancer.

Research on the treatment of cancer of unknown primary

Because CUP represents different types of cancer, it’s unlikely that a single treatment breakthrough will help all people with CUP. Still, progress in treating some of the more common types of cancer is likely to benefit people with CUP as well, especially if the cancers can be classified more accurately.

Targeted mutations

As researchers have come to understand the genetic changes that cause these tumors, they have been able to use newer treatments to target these changes.

As targeted treatments are found for more of the specific molecular changes in cancer cells, knowing the origin of a cancer may become less important. Detailed information about changes in the cancer cells’ DNA and RNA may become more important in choosing the treatments most likely to help individual patients.

Immunotherapy

Progress in immunotherapy, which uses the body’s immune system to attack cancer cells, has been made in many different cancer types. Researchers have identified targetable surface markers that can indicate a likelihood that cancer will respond to immunotherapy. This can help guide physicians in treating patients with CUP who would most benefit from immunotherapy.

Clinical trials

Many patients with CUP face a serious prognosis. Clinical trials are needed to increase treatment options. Some of these trials are testing new chemotherapy drugs, new drug combinations, and new ways to give these drugs. Other clinical trials are studying new approaches to treatment, such as biological therapy and gene therapy. Because CUP  can be many types of cancers, progress is likely to depend on continued progress toward understanding the molecular basis of all cancers.