Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation

• Type: Another Publication in an International Scientific Journal
• Date: 2016

Authors

Ferreira, JA (Author) Other; Peixoto, A (Author) Other; Neves, M (Author) Other; Gaiteiro, C (Author) Other; Celso Reis (Author) ICBAS; Assaraf, YG (Author) Other; Santos, LL (Author) Other

Journal

Title: Drug Resistance Updates

Vol. 24

Pages: 34-54

ISSN: 1368-7646

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 99 Citations

Scopus - 102 Citations

Other information

Authenticus ID: P-00K-3VF

DOI: 10.1016/j.drup.2015.11.003

Abstract (EN): Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omits models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 21