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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 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 for doctors to be able to identify the origin of cancers of unknown primary so that the most effective treatments can be used. Immunohistochemistry and tumor genomic profiling (also known as next generation sequencing of the tumor) can be very helpful in this regard, but they are not yet able to tell where all cancers of unknown primary (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.
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.
In addition to identifying "targetable mutations" in the DNA of cancer cells, testing for the cancer cell's PD-L1 expression and tumor mutational burden may also be important. These results an be used? when making decisions about the risks and benefits of immunotherapy treatment. While immunotherapy (either with or without chemotherapy) is commonly used for many cancer types, it continues to be an area of active research for CUP.
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 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 oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.
Greco FA, Hainsworth JD. Carcinoma of Unknown Primary In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2015: 1719-1736.
National Cancer Institute. Physician Data Query (PDQ). Cancer of Unknown Primary Treatment. 05/6/2024. Accessed at: https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq on May 20, 2024.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Occult Primary. v.2.2024. Accessed at https://www.nccn.org on May 20, 2024.
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Posner A, Sivakumaran T, Pattison A, Etemadmoghadam D, Thio N, Wood C, Fisher K, Webb S, DeFazio A, Wilcken N, Gao B, Karapetis CS, Singh M, Collins IM, Richardson G, Steer C, Warren M, Karanth N, Fellowes A, Fox SB, Hicks RJ, Schofield P, Bowtell D, Prall OWJ, Tothill RW, Mileshkin L. Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary. J Immunother Cancer. 2023 Jan;11(1):e005809. doi: 10.1136/jitc-2022-005809. PMID: 36720497; PMCID: PMC10098268.
Sheng J, Pan H, Han W. Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature. Front Immunol. 2023 Apr 19;14:1181444. doi: 10.3389/fimmu.2023.1181444. PMID: 37153561; PMCID: PMC10154565.
Varadhachary GR, Lenzi R, Raber MN, Abbruzzese JL. Carcinoma of Unknown Primary In: Neiderhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. 础产别濒辞蹿蹿’蝉 Clinical Oncology. 5th ed. Philadelphia, PA. Elsevier: 2014:1792-1803.
Last Revised: May 29, 2024
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