TITLE:
Targeting Transforming Growth Factor-β (TGF-β) in Cancer and Non-Neoplastic Diseases
AUTHORS:
Michael Nacif, Olfat Shaker
KEYWORDS:
Transforming Growth Factor-β (TGF-β), Monoclonal Antibodies (MoAbs), Antisense Oligonucleotides (ASO), Small Molecule Receptor Kinase Inhibitors (SMIs)
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.7,
June
24,
2014
ABSTRACT:
Transforming growth
factor-β(TGF-β)
superfamily is a key player in the regulation of a wide variety of
physiological processes from development to pathogenesis. Since the discovery
of the prototypic member, TGF-β, almost three decades ago, there have
been tremendous advances in our understanding of its complex biology. TGF-βmisregulation has been implicated in
the pathogenesis of a variety of diseases, including cancer with a direct role
in facilitating metastasis, fibrosis and inflammation. Consequently, TGF-βis currently explored as a prognostic
candidate biomarker of tumor invasiveness and metastasis; and it offers an
attractive target for cancer therapy. Several anti-TGF-βapproaches, such as TGF-βantibodies, antisense oligonucleotides
and small molecules inhibitors of TGF-βtype 1 receptor kinase, have shown
great promise in the preclinical studies. Here, we consider why the TGF-βsignaling
pathway is a drug target, the potential clinical applications of TGF-βinhibition, the issues arising with
anti-TGF-βtherapy and how
these might be adopted using personalized approaches with a special care for
patient selection and timing of therapy so that we may bring forward all the
potentials of targeting this pathway for therapeutic uses in both cancer,
preferentially in combination therapy, and non-neoplastic diseases.