New Tests May Find Treatments for Carcinoma of Unknown Primary (CUP)

A recent article published in Cancer Research UK informs readers that in two out of every one hundred cancers, doctors cannot find the original tumor. It is this primary tumor that generally dictates the appropriate treatment. Therefore, carcinoma of unknown primary (CUP) remains the fifth leading cause of cancer death in the United Kingdom.

The First Signs of Cancer Leading to CUP

Due to the absence of an original tumor, doctors may not be able to diagnose CUP until the cancer has advanced. It is well known that guidelines for cancer treatment depend on, among other things, the appearance of the primary tumor under a microscope.

According to Dr. Natalie Cook, a cancer specialist at the Christie Hospital in Manchester and clinical lead for the Manchester Experimental Cancer Medicine Centre, symptoms do not develop until the cancer has spread, so that many patients arrive at her clinic with advanced stages of cancer.

“A lot of cancers have good amounts of tissue to work with, either from biopsies or when a patient has had surgery.” says Cook. She goes on to explain that the samples may then be used for various diagnostic tests and their results used to guide treatment.

However, the materials available to doctors after a CUP diagnosis are limited according to Cook.

“The problem with CUP is that we only have small biopsies from the potential sites where the cancer has spread to, which can be quite difficult.” – Dr. Natalie Cook

“Chemotherapy is usually the only treatment option and once people have relapsed on chemotherapy there really is no standard option.” Cook explains that for this reason collecting more information on these cancers is crucial.

Scientists use tissue samples to study cancer and to find ways to put it into remission or bring about a cure. In the British Journal of Cancer, Cook and her colleagues lay out the challenges facing them when they do not have the benefit of being able to identify the original tissue. Yet this does not deter them from exploring new ways in which research can understand CUP and help in conducting future treatment.

CUP Affects Any Age Group

“You’re already quite anxious, angry, upset – all of those feelings you get with a cancer diagnosis anyway – but then when you can’t treat it because you don’t know where it is, its a lot more frustrating.”

These feelings were expressed by Beth, who was diagnosed with cancer of unknown primary at the age of 22. (CUP usually affects older people.)

“If you’ve already dealt with one diagnosis, in my case, brain cancer, you already start wondering: ‘Am I going to deal with a liver one, or a kidney one, or something else in the future?’ says Beth.

Experts in CUP research believe that a portion of the original cancer may have either shrunk or remained small. This would leave patients faced with the risk of tumor growth or reappearance of the primary tumor or even metastasizing (spreading).

Liquid Biopsies Find Clues in the Blood

The first step in diagnosing CUP is to develop improved methods of working with the limited amount of tissue available.  The second step is working with the tumor cells or cancer DNA that has spilled into a patient’s bloodstream. He believes that they hold genetic information which could decode the origin of the cancer and expand a CUP patient’s options.

Cook and her team are working with liquid biopsy expert Professor Caroline Dive, from the Cancer Research UK Manchester Institute with the support of Biomedical Research Center funding to develop liquid biopsies of CUP patients and to profile the genetic makeup of their tumors.

One of the academic clinical trials now underway is called Target. This involves analyzing the DNA in CUP patients’ blood to determine whether there are cancer-related changes in their DNA. This enables the team to determine if they have access to a drug that would target that molecular change.

Clinical trials in England, once they have proved that they are effective for a specific primary cancer, are approved by the National Health Service (NHS). For CUP, which categorizes several origins of cancers under ‘unknown’ it is difficult to find effective treatment.

As a result of a worldwide trial due to complete in 2022, CUP patients will have access to a range of drugs.  These drugs will be administered in accordance with the genetic composition of their tumors. The outcome of the trial may result in more personalized treatment for CUP.

Researchers, such as Professor Dive, Dr. Cook and their teams, are working to improve their understanding of CUP and to investigate genetic changes that affect the behavior of cancer and the interaction of CUP tumors with the immune system. Most importantly, they are looking at patterns in molecular profiles that would predict CUP’s origins.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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