Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives

Abstract

Abstract:The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a role in carcinogenesis as recognition patterns for galectins. Galectins are members of the lectin family, which show high affinity for β-galactosides. The galectin-glycan conjugate plays a fundamental role in metastasis, angiogenesis, tumor immunity, proliferation and apoptosis. Galectins' action is mediated by a structure containing at least one carbohydrate recognition domain (CRD). The potential prognostic value of galectins has been described in several neoplasms and helps clinicians predict disease outcome and determine therapeutic interventions. Currently, new therapeutic strategies involve the use of inhibitors such as competitive carbohydrates, small non-carbohydrate binding molecules and antibodies. This review outlines our current knowledge regarding the mechanism of action and potential therapy implications of galectins in cancer.

High intratumoural galectin‐1 expression predicts adverse outcome in ALK− ALCL and CD30+ PTCL‐NOS

“…Interestingly, increased Gal‐1 expression has been associated with poor prognosis and tumour metastasis in most tumour types analysed . Indeed, Gal‐1‐specific inhibitors and antibodies have been developed, and a clinical phase I trial testing the efficacy of the Gal‐1 inhibitor OTX008 to patients with advanced solid tumours is ongoing …”

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

“…Abnormal expression of tumor-associated galectins correlates with the development, progression and clinical aggressiveness of the tumors, as well as the contribution to metastatic phenotype [54,[126][127][128][129][130][131]. Tumor-derived galectins have opposite functions on different immune cells that either promote inflammation or decrease immune responses, depending on the inflammatory environment among tumor cells.…”

“…This means that the tumor-derived galectins have bipotential consequences on both tumor and immune cells [130]. Thus, new therapeutic strategies may be designed to facilitate the use of galectins as biological response modifiers to either tumor cells or immune cells [54,129,131].…”

Galectin 1 in dermatology: current knowledge and perspectives

“…Galectins constitute a family of β-galactoside-binding lectins that possess one or two unique structures termed "conserved carbohydrate-recognition domains" (CRDs), by means of which they bind with diverse carbohydrate ligands (4,5). Nineteen mammalian galectins (13 in humans) have so far been identified (6), most of which consist of one CRD with a highly conserved amino acid sequence and a β-sandwich structure (characterized by two opposing antiparallel β-sheets), whereas a few others contain two homologous CRDs separated by a linker of up to 70 amino acids (4). Based on their structural properties, galectins can be classified into three major subfamilies: 1.…”