Revving up metabolism at ASH 2018
A dive into the ASH 2018 abstracts highlights cancer metabolism as a top focus
Cancer metabolism is a prominent theme at this year’s ASH meeting, with researchers broadening the tent from metabolic targets that drive hematologic malignancies to those that intersect with other hot topics, notably immuno-oncology and epigenetics.
BioCentury’s survey of 4,355 abstracts from this year’s meeting of the American Society of Hematology, which takes place Dec. 1- 4 in San Diego, identifies 77 new and emerging targets, documents new cell types being engineered to treat cancer and finds rising preclinical activity in multiple myeloma (MM).
Cancer metabolism emerges as a recurrent theme across modalities, indications and new and established targets.
At least 300 abstracts discuss cancer metabolism or targets associated with cancer metabolism, over 100 discuss cell therapies and over 300 cover epigenetics, and those three themes overlap in many of the abstracts.
Clinical headlines in cancer metabolism, both positive and negative, are likely behind much of the interest.
The last 18 months saw approvals for the first two drugs founded on the hypothesis that altered cellular metabolism contributes to tumorigenesis. Agios Pharmaceuticals Inc.’s Idhifa enasidenib and Tibsovo ivosidenib are both marketed for acute myelogenous leukemia (AML).
While Incyte Corp.’s Phase III failure in April of IDO1 antagonist epacadostat set back interest in that target, it piqued stakeholder appetite for finding and validating new targets in the immuno-metabolism space -- a division of the field that aims to modify immune cells to increase their ability to fight cancer (see “Raising Metabolism”).
This year’s abstracts contain at least 27 metabolic targets, over half of which play into immuno-metabolism (see “Table: Cancer Metabolism Targets at ASH”).
Table: Cancer metabolism targets at ASH
Cancer metabolism emerged as a dominant theme at the 2018 meeting of the American Society of Hematology (ASH). At least 27 targets with known metabolic function and links to cancer were discussed in at least one abstract. Source: ASH 2018 Abstracts; BCIQ: BioCentury Online Intelligence
|Pathway||Target||Number of abstracts|
|Adenosine pathway||Ecto-5'-nucleotidase (NT5E; CD73)||10|
|Ectonucleoside triphosphate diphosphohydrolase 1 (CD39; ENTPD1)||10|
|Adenosine A2B receptor (ADORA2B)||1|
|Amino acid metabolism||Thymidylate synthetase (TYMS)||1|
|Arginine pathway||Arginase 1 (ARG1)||8|
|Nitric oxide synthase||3|
|Inducible nitric oxide synthase 2 (NOS2; iNOS)||6|
|Fatty acid synthesis||Acetyl-Coenzyme A carboxylase α (ACACA; ACC1)||3|
|Fatty acid synthase (FASN; FAS)||3|
|ATP citrate lyase (ACLY)||2|
|Glutamine pathway||Glutaminase (GLS)||3|
|Glutathione peroxidase (GPX)||3|
|Glutathione peroxidase 1 (GPX1)||3|
|Glycolysis||Solute carrier family 2 facilitated glucose transporter member 1 (SLC2A; GLUT1)||4|
|Glucose-6-phosphate dehydrogenase (G6PD)||8|
|Prostacyclin receptor (PGI2; PTGIR)||1|
|Krebs cycle||Isocitrate dehydrogenase 1 (IDH1)||102|
|Mitochondrial biogenesis||CCAAT enhancer binding protein α (CEBPA)||63|
|Peroxisome proliferation activated receptor γ coactivator 1-α (PGC-1α; PPARGC1A)||5|
|Nucleic acid synthesis||Ribonucleotide reductase M2 (RRM2; R2)||3|
|Tryptophan metabolism||Aryl hydrocarbon receptor|