title: Low Beclin-1 expression predicts improved overall survival in patients treated with immunomodulatory drugs for multiple myeloma and identifies autophagy inhibition as a promising potentially druggable new therapeutic target: an analysis from The Austrian Myeloma Registry (AMR).
abstract: Beclin-1 is a key regulator of autophagy and has been suggested to be involved in the development of drug resistance in multiple myeloma (MM). We analyzed the expression of Beclin-1 in a retrospective cohort of 70 MMs. Beclin-1 expression did not influence overall survival (OS) and progression-free survival (PFS) in patients with therapy-naïve MM. In patients treated with immunomodulatory drugs (IMiDs) lack of or low Beclin-1 expression resulted in a significantly improved OS and PFS compared to those treated with bortezomib or nonnovel agents. Beclin-1 expression was more frequently detected in relapsed MM than in therapy-naïve MM probably being a hallmark of tumor progression and therapy resistance. If validated prospectively, Beclin-1 expression might identify patients prone to profit above average from IMiDs and enable a more rational allocation of antimyeloma therapies. Furthermore, the inhibition of autophagy could be a new promising target to improve response to treatment in the relapsed/refractory setting.
authors.affiliation: a Department of Internal Medicine , University Hospital for Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck , Innsbruck , Austria ;|b Area 4 Health Technology Assessment and Bioinformatics , ONCOTYROL - Center for Personalized Cancer Medicine , Innsbruck , Austria ;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Willenbacher
authors.affiliation: c Tyrolean Cancer Research Institute , Innsbruck , Austria ;
authors.forename: Shanmugapriya
authors.initials: S
authors.lastname: Thangavadivel
authors.affiliation: c Tyrolean Cancer Research Institute , Innsbruck , Austria ;|d Laboratory of Immunological and Molecular Cancer Research , Salzburg Cancer Research Institute , Salzburg , Austria ;
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: a Department of Internal Medicine , University Hospital for Internal Medicine V (Haematology and Oncology), Medical University of Innsbruck , Innsbruck , Austria ;
authors.forename: Ella
authors.initials: E
authors.lastname: Willenbacher
authors.affiliation: b Area 4 Health Technology Assessment and Bioinformatics , ONCOTYROL - Center for Personalized Cancer Medicine , Innsbruck , Austria ;
authors.forename: Roman
authors.initials: R
authors.lastname: Weger
authors.affiliation: e Department of Pathology, Division of General Pathology , Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Manzl
authors.affiliation: c Tyrolean Cancer Research Institute , Innsbruck , Austria ;
authors.forename: Karin
authors.initials: K
authors.lastname: Jöhrer
authors.affiliation: e Department of Pathology, Division of General Pathology , Medical University of Innsbruck , Innsbruck , Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D018450:Disease Progression; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000071186:Beclin-1; D015415:Biomarkers; D007155:Immunologic Factors
keywords: Autophagy; Beclin-1; IMiDs; biomarkers; multiple myeloma