AXL - a new player in resistance to HER2 blockade
Adam-Artigues, Anna (INCLIVA Biomedical Research Institute)
Arenas, Enrique J (Centro de Investigación Biomédica en Red de Cáncer)
Arribas, Joaquín V (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Prat, Aleix (SOLTI Breast Cancer Research Group)
Cejalvo, Juan Miguel (Vall d'Hebron Institut d'Oncologia)

Data:	2023
Resum:	HER2 is a driver in solid tumors, mainly breast, oesophageal and gastric cancer, through activation of oncogenic signaling pathways such as PI3K or MAPK. HER2 overexpression associates with aggressive disease and poor prognosis. Despite targeted anti-HER2 therapy has improved outcomes and is the current standard of care, resistance emerge in some patients, requiring additional therapeutic strategies. Several mechanisms, including the upregulation of receptors tyrosine kinases such as AXL, are involved in resistance. AXL signaling leads to cancer cell proliferation, survival, migration, invasion and angiogenesis and correlates with poor prognosis. In addition, AXL overexpression accompanied by a mesenchymal phenotype result in resistance to chemotherapy and targeted therapies. Preclinical studies show that AXL drives anti-HER2 resistance and metastasis through dimerization with HER2 and activation of downstream pathways in breast cancer. Moreover, AXL inhibition restores response to HER2 blockade in vitro and in vivo. Limited data in gastric and oesophageal cancer also support these evidences. Furthermore, AXL shows a strong value as a prognostic and predictive biomarker in HER2+ breast cancer patients, adding a remarkable translational relevance. Therefore, current studies enforce the potential of co-targeting AXL and HER2 to overcome resistance and supports the use of AXL inhibitors in the clinic.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Ressenya ; recerca ; Versió publicada
Matèria:	HER2 disease ; Cancer ; AXL ; Resistance
Publicat a:	Cancer Treatment Reviews, Vol. 121 (december 2023) , p. 102639, ISSN 1532-1967

DOI: 10.1016/j.ctrv.2023.102639

8 p, 1.2 MB

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