Identifying disease-causing mechanisms in cancer of unknown primary improves treatment

Both treatment and survival are improved when a tumor whose primary site is unknown has its molecular profile identified. This research was presented at the 2013 European Cancer Congress in Amsterdam, The Netherlands.

The site of the primary tumor is unknown in up to 5% of all cancers, and the disease is not diagnosed until the cancer is at an advanced stage, when it has metastasized. Until recently, treatment choice is based on biomarkers that could indicate the site of origin; however, now a team of researchers has succeeded in identifying the particular molecular profiles of metastatic tumors in a large group of patients. The research team, led by Zoran Gatalica, MD, DSc, of Caris Life Sciences in Phoenix, Arizona, and of Creighton University School of Medicine, explained that this is a major step on the road to being able to offer effective treatments to these patients.

"Previous attempts to characterize cancer of unknown primary (CUP) have only managed to provide a statistical likelihood of a potential primary organ site, and for the most part have not addressed the question of whether a particular treatment is likely to be effective,” said Gatalica. The research team set out to do just that in a large group of more than 1,350 patients with CUP. Gatalica reports that this is the largest group to date to have their molecular profiles characterized.

Using a number of different molecular methods to assess the expression of biomarkers associated with the potential for drug response, the researchers were able to find targets for which there are existing cancer drugs in 77% of the tumors profiled.

Not knowing the primary site of the cancer creates uncertainty in the selection of optimal treatment. Recent advances in translational medicine and cancer molecular profiling have shown that different cancers may share the same molecular pathways, which provides the biological basis for utilizing the same, targeted therapy in many different cancer types, irrespective of primary site. This advance in the understanding of cancer biology has allowed researchers to take the novel approach of looking for commonly altered cancer pathways in a group of patients with CUP.

Providing information on the potential benefit as well as the potential lack of benefit for a variety of oncology drugs in the context of the patient's unique cancer molecular profile and overall clinical circumstances can provide the oncologist with critical information that will help them to select optimal treatment. Additionally, the molecular profiling of a tumor may allow for patients with CUP to enroll in trials designed around that molecular profile.

"We believe that our research signals a paradigm shift in the treatment of CUP, from treatment based on an attempt to define the location of the primary site to treatment based on the biology of the tumour, and that, as more targets and targeted therapies are discovered, the chances of finding those that will benefit individual patents will increase," concluded Gatalica.

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