Precision autophagy: Will the next wave of selective autophagy markers and specific autophagy inhibitors feed clinical pipelines?
Research presented at the Vancouver Autophagy Symposium (VAS) 2014 suggests that autophagy's influence on health and disease depends on tight regulation and precision targeting of substrates. Discussions recognized a pressing need for robust biomarkers that accurately assess the clinical utility of modulating autophagy in disease contexts. Biomarker discovery could flow from investigations of context-dependent triggers, sensors, and adaptors that tailor the autophagy machinery to achieve target specificity. In his keynote address, Dr. Vojo Deretic (University of New Mexico) described the discovery of a cargo receptor family that utilizes peptide motif-based cargo recognition, a mechanism that may be more precise than generic substrate tagging. The keynote by Dr. Alec Kimmelman (Harvard Medical School) emphasized that unbiased screens for novel selective autophagy factors may accelerate the development of autophagy-based therapies. Using a quantitative proteomics screen for de novo identification of autophagosome substrates in pancreatic cancer, Kimmelman's group discovered a new type of selective autophagy that regulates bioavailable iron. Additional presentations revealed novel autophagy regulators and receptors in metabolic diseases, proteinopathies, and cancer, and outlined the development of specific autophagy inhibitors and treatment regimens that combine autophagy modulation with anticancer therapies. VAS 2014 stimulated interdisciplinary discussions focused on the development of biomarkers, drugs, and preclinical models to facilitate clinical translation of key autophagy discoveries.
a The Genome Sciences Centre; BC Cancer Agency ; Vancouver , BC Canada.|b Department of Molecular Biology and Biochemistry, Simon Fraser University ; Burnaby , BC Canada.
Chandra B
CB
Lebovitz
c Deeley Research Centre; BC Cancer Agency ; Victoria , BC Canada.
Lindsay
L
DeVorkin
d Department of Chemistry, Simon Fraser University ; Burnaby , BC Canada.
Damien
D
Bosc
e Terry Fox Laboratory; BC Cancer Agency ; Vancouver , BC Canada.|f Department of Medical Genetics, University of British Columbia ; Vancouver , BC Canada.
Katharina
K
Rothe
g Department of Experimental Therapeutics, BC Cancer Agency ; Vancouver , BC Canada.|h Department of Pathology and Laboratory Medicine, University of British Columbia ; Vancouver , BC Canada.
Jagbir
J
Singh
g Department of Experimental Therapeutics, BC Cancer Agency ; Vancouver , BC Canada.|h Department of Pathology and Laboratory Medicine, University of British Columbia ; Vancouver , BC Canada.|i The Centre for Drug Research and Development ; Vancouver , BC Canada.
Marcel
M
Bally
e Terry Fox Laboratory; BC Cancer Agency ; Vancouver , BC Canada.|f Department of Medical Genetics, University of British Columbia ; Vancouver , BC Canada.
Xiaoyan
X
Jiang
d Department of Chemistry, Simon Fraser University ; Burnaby , BC Canada.|i The Centre for Drug Research and Development ; Vancouver , BC Canada.
Robert N
RN
Young
c Deeley Research Centre; BC Cancer Agency ; Victoria , BC Canada.
Julian J
JJ
Lum
a The Genome Sciences Centre; BC Cancer Agency ; Vancouver , BC Canada.|b Department of Molecular Biology and Biochemistry, Simon Fraser University ; Burnaby , BC Canada.
Sharon M
SM
Gorski
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D040901:Proteomics / Q000379:methods
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D002352:Carrier Proteins
LC3; SQSTM1; TRIM; autophagy, biomarker; cancer; hydroxychloroquine; neurodegeneration; pancreatic cancer; selective autophagy