Galectins as Emerging Glyco-Checkpoints and Therapeutic Targets in Glioblastoma

GUILLERMO A. VIDELA-RICHARDSON ; OLIVIA MORRIS-HANON ; NICOLÁS I. TORRES ; MYRIAN I. ESQUIVEL ; MARIANA B. VERA ; LUISINA B. RIPARI ; DIEGO O. CROCI ; GUSTAVO E. SEVLEVER ; GABRIEL A. RABINOVICH

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2021 vol. 23

1422-0067

Abstract: Despite recent advances in diagnosis and treatment, glioblastoma (GBM) represents themost common and aggressive brain tumor in the adult population, urging identification of newrational therapeutic targets. Galectins, a family of glycan-binding proteins, are highly expressed inthe tumor microenvironment (TME) and delineate prognosis and clinical outcome in patients withGBM. These endogenous lectins play key roles in different hallmarks of cancer by modulatingtumor cell proliferation, oncogenic signaling, migration, vascularization and immunity. Additionally, they have emerged as mediators of resistance to different anticancer treatments, includingchemotherapy, radiotherapy, immunotherapy, and antiangiogenic therapy. Particularly in GBM,galectins control tumor cell transformation and proliferation, reprogram tumor cell migration andinvasion, promote vascularization, modulate cell death pathways, and shape the tumor-immunelandscape by targeting myeloid, natural killer (NK), and CD8+ T cell compartments. Here, wediscuss the role of galectins, particularly galectin-1, -3, -8, and -9, as emerging glyco-checkpointsthat control different mechanisms associated with GBM progression, and discuss possible therapeutic opportunities based on inhibition of galectin-driven circuits, either alone or in combinationwith other treatment modalities.