Τίτλος:
Activin receptor antagonists for cancer-related anemia and bone disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: Antagonists of activin receptor signaling may be
beneficial for cancer-related anemia and bone disease caused by
malignancies such as multiple myeloma and solid tumors.
Areas covered: We review evidence of dysregulated signaling by activin
receptor pathways in anemia, myeloma-associated osteolysis, and
metastatic bone disease, as well as potential involvement in
carcinogenesis. We then review properties of activin receptor
antagonists in clinical development.
Expert opinion: Sotatercept is a novel receptor fusion protein that
functions as a soluble trap to sequester ligands of activin receptor
type IIA (ActRIIA). Preclinically, the murine version of sotatercept
increased red blood cells (RBC) in a model of chemotherapy-induced
anemia, inhibited tumor growth and metastasis, and exerted anabolic
effects on bone in diverse models of multiple myeloma. Clinically,
sotatercept increases RBC markedly in healthy volunteers and patients
with multiple myeloma. With a rapid onset of action differing from
erythropoietin, sotatercept is in clinical development as a potential
first-in-class therapeutic for cancer-related anemia, including those
characterized by ineffective erythropoiesis as in myelodysplastic
syndromes. Anabolic bone activity in early clinical studies and
potential antitumor effects make sotatercept a promising therapeutic
candidate for multiple myeloma and malignant bone diseases. Antitumor
activity has been observed preclinically with small-molecule inhibitors
of transforming growth factor-beta receptor type I (ALK5) that also
antagonize the closely related activin receptors ALK4 and ALK7.
LY-2157299, the first such inhibitor to enter clinical studies, has
shown an acceptable safety profile so far in patients with advanced
cancer. Together, these data identify activin receptor antagonists as
attractive therapeutic candidates for multiple diseases.
Συγγραφείς:
Fields, Scott Z.
Parshad, Shiroo
Anne, Madhurima and
Raftopoulos, Haralambos
Alexander, Mark J.
Sherman, Matthew L.
and Laadem, Abderrahmane
Sung, Victoria
Terpos, Evangelos
Περιοδικό:
Expert Opinion on Investigational Drugs
Εκδότης:
TAYLOR & FRANCIS LTD LONDON
Λέξεις-κλειδιά:
ACE-011; ActRIIA; erythropoietin; LY-2157299; multiple myeloma;
sotatercept
DOI:
10.1517/13543784.2013.738666
