EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?
| Autor: | Vito Michele Fazio, Mario Cioce |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer EGFR ephrins inter-tumor heterogeneity Review EphA2 lcsh:RC254-282 Receptor tyrosine kinase law.invention 03 medical and health sciences 0302 clinical medicine law cetuximab medicine Ephrin drug resistance biology Cetuximab business.industry Erythropoietin-producing hepatocellular (Eph) receptor Cancer intra-tumor heterogeneity medicine.disease EPH receptor A2 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens TKI CRC 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research CSCs Suppressor business medicine.drug |
| Zdroj: | Cancers, Vol 13, Iss 700, p 700 (2021) Cancers Cancers (Basel) 13 (2021): 1–23. doi:10.3390/cancers13040700 info:cnr-pdr/source/autori:Cioce M.; Fazio V.M./titolo:Epha2 and egfr: Friends in life, partners in crime. can epha2 be a predictive biomarker of response to anti-egfr agents?/doi:10.3390%2Fcancers13040700/rivista:Cancers (Basel)/anno:2021/pagina_da:1/pagina_a:23/intervallo_pagine:1–23/volume:13 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13040700 |
| Popis: | Simple Summary The Ephrin receptors and their ligands play important roles in organ formation and tissue repair, by orchestrating complex programs of cell adhesion and repulsion, however, this same system plays a role in cancer development In fact, EphA2 levels are higher in tumors vs normal tissue and further increased upon treatment, in vivo and in vitro. Changes in the molecular status of EphA2, of its subcellular localization, the absence of ligand and signals derived from the tumor context unleash the oncogenic role of EphA2 and its broad ability to promote resistance to radiotherapy, chemotherapy and targeted agents, including inhibitors of Epidermal-Growth-Factor-Receptor (EGFR). High levels of EphA2 may reduce response to cetuximab even in RAS wt CRC patients. In this work, we aim to review the current knowledge of the EphA2 function which is crucial for achieving a more effective therapeutic management of tumors resistant to EGFR inhibitors and to many other agents. Abstract The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC); however, what causes EphA2 to switch between tumor-suppressive and tumor-promoting function is still an active theater of investigation. This review summarizes the recent advances in understanding EphA2 function in cancer, with detail on the molecular determinants of the oncogene-tumor suppressor switch function of EphA2. We describe tumor context-specific examples of EphA2 signaling and the emerging role EphA2 plays in supporting cancer—stem—cell-like populations and overcoming therapy-induced stress. In such a frame, we detail the interaction of the EphA2 and EGFR pathway in solid tumors, including colorectal cancer. We discuss the contribution of the EphA2 oncogenic signaling to the resistance to EGFR blocking agents, including cetuximab and TKIs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|