Towards a more precise therapy in cancer: Exploring epigenetic complexity
Por:
Cossio, FP, Esteller, M and Berdasco, M
Publicada:
1 ago 2020
Resumen:
A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the chemical design, the biological rationale and the clinical trial development of epidrugs. Specifically, we focus on the development of dual hybrids to exploit multitargeting of key epigenetic molecules deregulated in cancer; the study of epigenetic-synthetic lethality interactions as a mechanism to address loss-of-function mutations, and the combination of epidrugs with other therapies such as immunotherapy to avoid acquired chemoresistance and increase therapy sensitivity. By exploring these challenges, among others, the field of epigenetic chemical biology will increase its potential for clinical benefit, and more effective strategies targeting the aberrant epigenome in cancer are likely to be developed both in haematological and solid tumours.
Filiaciones:
Cossio, FP:
Univ Pais Vasco Euskal Herriko Unibertsitaea, Kim Fak, Kim Organ & Saila, Donostia San Sebastian, Spain
Donostia Int Phys Ctr DIPC, Donostia San Sebastian, Spain
Ctr Innovac Quim Avanzada ORFEO CINQA, Zaragoza, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc Epigenet Grp, Canc & Leukemia Epigenet & Biol Program PEBCL, Barcelona, Catalonia, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Catalonia, Spain
Univ Barcelona, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Catalonia, Spain
:
Bellvitge Biomed Res Inst IDIBELL, Barcelona, Catalonia, Spain
Josep Carreras Leukaemia Res Inst IJC, Expt & Clin Hematol Program PHEC, Epigenet Therapies Grp, Badalona, Catalonia, Spain
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