Next Article in Journal
The Effect of Aspirin on Preventing Vascular Access Dysfunction in Incident Hemodialysis Patients: A Prospective Cohort Study in Korean Clinical Research Centers for End-Stage Renal Disease (CRC for ESRD)
Next Article in Special Issue
Phosphoproteomic Profiling Identifies Aberrant Activation of Integrin Signaling in Aggressive Non-Type Bladder Carcinoma
Previous Article in Journal
Stem Cells in Equine Veterinary Practice—Current Trends, Risks, and Perspectives
Previous Article in Special Issue
Control of Invasion by Epithelial-to-Mesenchymal Transition Programs during Metastasis
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessReview

Contribution of Epithelial Plasticity to Therapy Resistance

Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPAZ, c/ Arzobispo Morcillo 4, 28029 Madrid, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), c/ Monforte de Lemos 3-5, 28029 Madrid, Spain
Fundación MD Anderson Internacional, c/ Gómez Hemans 2, 28033 Madrid, Spain
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(5), 676;
Received: 15 April 2019 / Revised: 9 May 2019 / Accepted: 10 May 2019 / Published: 14 May 2019
PDF [503 KB, uploaded 14 May 2019]
  |     |  


Therapy resistance is responsible for tumour recurrence and represents one of the major challenges in present oncology. Significant advances have been made in the understanding of the mechanisms underlying resistance to conventional and targeted therapies improving the clinical management of relapsed patients. Unfortunately, in too many cases, resistance reappears leading to a fatal outcome. The recent introduction of immunotherapy regimes has provided an unprecedented success in the treatment of specific cancer types; however, a good percentage of patients do not respond to immune-based treatments or ultimately become resistant. Cellular plasticity, cancer cell stemness and tumour heterogeneity have emerged as important determinants of treatment resistance. Epithelial-to-mesenchymal transition (EMT) is associated with resistance in many different cellular and preclinical models, although little evidence derives directly from clinical samples. The recognition of the presence in tumours of intermediate hybrid epithelial/mesenchymal states as the most likely manifestation of epithelial plasticity and their potential link to stemness and tumour heterogeneity, provide new clues to understanding resistance and could be exploited in the search for anti-resistance strategies. Here, recent evidence linking EMT/epithelial plasticity to resistance against conventional, targeted and immune therapy are summarized. In addition, future perspectives for related clinical approaches are also discussed. View Full-Text
Keywords: epithelial–mesenchymal transition; hybrid E/M states; plasticity; tumour heterogeneity; treatment resistance; immunotherapy scape epithelial–mesenchymal transition; hybrid E/M states; plasticity; tumour heterogeneity; treatment resistance; immunotherapy scape

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Santamaría, P.G.; Moreno-Bueno, G.; Cano, A. Contribution of Epithelial Plasticity to Therapy Resistance. J. Clin. Med. 2019, 8, 676.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top