title: Increase in antibody-dependent cellular cytotoxicity (ADCC) in a patient with advanced colorectal carcinoma carrying a KRAS mutation under lenalidomide therapy.
abstract: The failure of EGFR inhibitors in colorectal tumors with KRAS mutations requires the development of alternative treatment strategies for this patient subgroup. Among the hallmarks of cancer the disturbed immunosurveillance and cancer immune evasion have become emerging targets for cancer therapy. Due to their pleiotropic functions immunomodulatory drugs (IMiDs) are interesting agents for combination therapies in solid tumors. However, their possible contribution and a way of monitoring their biological effects have yet to be revealed. In a heavily pretreated patient with advanced colorectal cancer carrying mutations in APC and KRAS genes, we show an early metabolic response and enhanced NK cell activity to monotherapy with lenalidomide. After subsequent lenalidomide/cetuximab combination treatment, the patient had progressive disease. At the same time a reduced performance status, complicated by febrile neutropenia, occurred, as well as a slight increase in metabolic activity. Concordantly NK cell activity dropped back to baseline. Thus, laboratory measurements and metabolic response assessment correlated with clinical conditions. This case report describes the feasibility and potential of a functional assessment of patient derived immune competent cells in combination with functional imaging for the detection of a biological response.
authors.affiliation: Clinic for Internal Medicine V; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gamerith
authors.affiliation: Clinic for Radiology; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Auer
authors.affiliation: Clinic for Internal Medicine V; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Arno
authors.initials: A
authors.lastname: Amann
authors.affiliation: Clinic for Radiology; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Putzer
authors.affiliation: Clinic for General and Surgical Intensive Care; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schenk
authors.affiliation: Clinic for Internal Medicine V; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kircher
authors.affiliation: Clinic for Internal Medicine V; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hilbe
authors.affiliation: Clinic for Internal Medicine V; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Zwierzina
authors.affiliation: Clinic for Internal Medicine VI; Innsbruck Medical University; Innsbruck, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Loeffler-Ragg
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications*; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D000077269:Lenalidomide; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D009154:Mutation; D010386:Pelvic Neoplasms / Q000556:secondary; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D013792:Thalidomide; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077269:Lenalidomide
keywords: advanced colorectal cancer; antibody-dependent cellular cytotoxicity; biologic response; functional imaging; immune therapy