Activin A: an emerging target for improving cancer treatment?

Figures & data

Figure 1. Expression and signaling mechanisms of activin A and intervention points for targeting approaches. The synthesis of activin subunits and activin receptors, the regulation of activin receptor binding at the plasma membrane as well as activin A-induced signaling routes via Smad-dependent and Smad-independent pathways. Intervention points that have been used for targeting activin A signaling in preclinical models or clinical trials are highlighted

Table 1. Therapeutic agents with activin signaling inhibition capacity that have been used in clinical trials in cancer patients

Agent	Type	Targets	Cancer types	Clinical phases	Comment
STM 434	Ligand trap	Ligands binding ActRIIB	Ovarian, fallopian tube, endometrial and other cancers	Phase I	Stable disease in granulosa cell ovarian cancer patients, increase in lean body mass [118]
Sotatercept	Ligand trap	Ligands binding ActRIIA	Multiple Myeloma, metastatic solid tumors	Phase I, phase II	Effect on bone formation and anemia [94,117]
Galunisertib	Kinase inhibitor	TGFBRI, ActRIB	Several cancer types including HCC, prostate and pancreatic cancer and glioblastoma	Phase I, phase II	Survival improvement in pancreatic cancer [124], combination trials with immunotherapeutics initiated in several cancers
TargomiR	microRNA mimic	miR-16 target genes	MPM	Phase I	acceptable safety profile and early signs of activity [125]

Figure 2. The multiple functions of activin A in cancer. Aspects of cancer development and progression for which a regulation by activin A has been demonstrated. Targeting activin A can be used to interfere with these processes

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