Assessment of folate receptor alpha and beta expression in selection of lung and pancreatic cancer patients for receptor targeted therapies
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Jiayin Shen1, Yingwen Hu1,2, Karson S. Putt2, Sunil Singhal3, Haiyong Han4, Daniel W. Visscher5, Linda M. Murphy6 and Philip S. Low1,2
1Department of Chemistry, Purdue University, West Lafayette, IN, USA
2Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA
3Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA USA
4Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, AZ, USA
5Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
6Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA
Philip S. Low, email: [email protected]
Keywords: folate receptor alpha; folate receptor beta; lung cancer; pancreatic cancer; tumor associated macrophages
Abbreviations: folate receptor (FR); tumor microarray (TMA)
Received: September 13, 2017 Accepted: November 19, 2017 Published: December 15, 2017
A number of folate receptor (FR) targeted small molecular drugs and monoclonal antibodies have been introduced into clinical trials to treat FR positive cancers. Because the therapeutic efficacy of these drugs depends prominently on the level of FR-α expression on the cancer cells, patients have been commonly selected for FR-targeted therapies based on the intensity of a folate-targeted radioimaging agent. Unfortunately, uptake of such imaging agents can be mediated by both major isoforms of the folate receptor, FR-α and FR-β. Logically, if the FR positive cell population in a tumor mass is dominated by FR-β positive macrophages, patients could be selected for therapy that have few FR-expressing cancer cells. Although several IHC studies have examined expression of either FR-α or FR-β, no study to date has investigated expression of both FR-α and FR-β in the same tumor mass. Herein, we utilize monoclonal antibodies specific for FR-α (mAb343) and FR-β (m909) to query each isoform’s expression in a range of cancers. We show that lung and pancreatic adenocarcinomas express the full spectrum of FR-α and FR-β combinations with ~76% of lung adenocarcinomas expressing both FR-α and FR-β while pancreatic cancers express primarily FR-β. Thus, while folate-targeted imaging of lung cancer patients might accurately reflect the expression of FR-α on lung cancer cells, imaging of pancreatic cancer patients could mislead a physician into treating a nonresponding patient. Overall, these data suggest that an independent analysis of both FR-α and FR-β should be obtained to predict the potential efficacy of a folate-targeted drug.
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