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

PathwayTargetNumber of abstracts
Adenosine pathwayEcto-5'-nucleotidase (NT5E; CD73)10
Ectonucleoside triphosphate diphosphohydrolase 1 (CD39; ENTPD1)10
Adenosine receptors4
Adenosine A2B receptor (ADORA2B)1
Adenosine kinase1
Amino acid metabolismThymidylate synthetase (TYMS)1
Arginine pathwayArginase 1 (ARG1)8
Nitric oxide synthase3
Inducible nitric oxide synthase 2 (NOS2; iNOS)6
Fatty acid synthesisAcetyl-Coenzyme A carboxylase α (ACACA; ACC1)3
Fatty acid synthase (FASN; FAS)3
ATP citrate lyase (ACLY)2
Glutamine pathwayGlutaminase (GLS)3
Glutathione peroxidase (GPX)3
Glutathione peroxidase 1 (GPX1)3
GlycolysisSolute carrier family 2 facilitated glucose transporter member 1 (SLC2A; GLUT1)4
Glucose-6-phosphate dehydrogenase (G6PD)8
Prostacyclin receptor (PGI2; PTGIR)1
Krebs cycleIsocitrate dehydrogenase 1 (IDH1)102
IDH283
Mitochondrial biogenesisCCAAT enhancer binding protein α (CEBPA)63
Peroxisome proliferation activated receptor γ coactivator 1-α (PGC-1α; PPARGC1A)5
Nucleic acid synthesisRibonucleotide reductase M2 (RRM2; R2)3
Tryptophan metabolismAryl hydrocarbon receptor

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