What's New in Cancer of Unknown Primary Research?

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 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).


It’s important that doctors are able to identify the origin of cancers of unknown primary so that the most effective treatments can be used. Immunohistochemistry and other lab tests can be very helpful in this regard, but they are not yet able to tell where all CUPs have started. Newer lab tests now becoming available, and others being studied, will help classify CUP more precisely and predict a patient’s prognosis and response to treatment.

Hopefully at some point in the future, the number of cancers of unknown primary will drop dramatically, as doctors will be able to test tumor samples and determine what types of cancer they are.


Because CUP represents a number of different types of cancer, it’s unlikely that a single treatment breakthrough will benefit 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.

As researchers have come to understand the genetic changes that cause these tumors, they’ve been able to use newer treatments to target these changes. Some of these newer drugs are called targeted therapies. These drugs have more selective effects than chemotherapy (chemo). Some of them, such as bevacizumab (Avastin®) and erlotinib (Tarceva®), are available to treat other cancers and have shown some activity in CUP.

Recent studies have found that cancers starting in each organ are not all the same. They can have different changes in their most important molecules and respond differently to treatments.

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. Instead, 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.

Cancer cells from CUP are sometimes tested in a lab to try to see which chemo drugs will be likely to work. Unfortunately, these tests don’t always do a good job of predicting the right chemo drugs to use and don't always tell which are most effective. Many doctors don’t find them very helpful.

Many patients with cancer of unknown primary face a serious prognosis, so the need for advances in treatment is obvious. Clinical trials of new treatments are essential if progress is to occur. Some of these trials are testing new chemo drugs, new drug combinations, and new ways to give these drugs. Other clinical trials are studying new approaches to treatment, such as biological therapy, immunotherapy, and gene therapy. Because CUP is many types of cancers, progress against CUP is likely to depend on continued progress toward understanding the molecular basis of all cancers.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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National Cancer Institute. Physician Data Query (PDQ). Cancer of Unknown Primary Treatment. 07/25/2015. Accessed at: https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq on February 9, 2018.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Occult Primary. v.1.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf on February 9, 2018.

Varadhachary GR, Lenzi R, Raber MN, Abbruzzese JL. Carcinoma of Unknown Primary In: Neiderhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA. Elsevier: 2014:1792-1803.

Last Medical Review: March 9, 2018 Last Revised: March 9, 2018

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