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International Journal of Respiratory Medicine

Volume 3

LUNG CANCER AND COPD

International Congress on

J u n e 2 5 - 2 6 , 2 0 1 8 | A m s t e r d a m , N e t h e r l a n d s

Laetitia Seguin et al., Int J Respir Med 2018, Volume 3

GALECTIN-3, A DRUGGABLE

VULNERABILITY FOR KRAS-ADDICTED

CANCERS

Laetitia Seguin, Camargo MF, Wettersten H, Kato S

Desgrosellier JS, Von Schalscha T, Elliott KC, Cosset E

Lesperance J, Weis SM

and

Cheresh DA

IRCAN, France

dentifying the molecular basis for cancer cell dependence on oncogenes

such as KRAS can provide new opportunities to target these addictions.

Here, we identify a novel role for the carbohydrate-binding protein galectin-3

as a lynchpin for KRAS dependence. By directly binding to the cell surface

receptor integrin αvβ3, galectin-3 gives rise to KRAS addiction by enabling

multiple functions of KRAS in anchorage-independent cells, including

formation of macropinosomes that facilitate nutrient uptake and ability to

maintain redox balance. Disrupting αvβ3/galectin-3 binding with a clinically

active drug prevents their association withmutant KRAS, thereby suppression

macropinocytosis while increasing reactive oxygen species to eradicate

αvβ3-expressing KRAS-mutant lung and pancreatic cancer patient-derived

xenografts and spontaneous tumors in mice. Our work reveals galectin-3 as a

druggable target for KRAS-addicted lung and pancreas cancers and indicates

integrin αvβ3 as a biomarker to identify susceptible tumors. There is a

significant unmet need for therapies targeting KRAS-mutant cancers. Here,

we identify integrin αvβ3 as a biomarker to identify mutant KRAS-addicted

tumors that are highly sensitive to inhibition of galectin-3, a glycoprotein that

binds to integrin αvβ3 to promote KRAS-mediated activation of AKT.

Laetitia Seguin is currently working as a post-

doctoral fellow in C Feral Laboratory Epithelial

homeostasis and tumorigenesis at IRCAN,

France. She has published many papers in the

reputed journals with the eminent authors. She

has a great publication in the peer reviewed con-

ference proceedings also.

BIOGRAPHY