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Sapio L, Salzillo A, Ragone A, et al. Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update. Cancers (Basel). 2020;12(11)doi: 10.3390/cancers12113166.
Sapio, L., Salzillo, A., Ragone, A., Illiano, M., Spina, A., & Naviglio, S. (2020). Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update. Cancers, 12(11), . https://doi.org/10.3390/cancers12113166
Sapio, Luigi, et al. "Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update." Cancers vol. 12,11 (2020). doi: https://doi.org/10.3390/cancers12113166
Sapio L, Salzillo A, Ragone A, Illiano M, Spina A, Naviglio S. Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update. Cancers (Basel). 2020 Oct 28;12(11). doi: 10.3390/cancers12113166. PMID: 33126560; PMCID: PMC7693618.
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Cancers (Basel). 2020 Oct 28;12(11). doi: 10.3390/cancers12113166.

Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update.

Cancers

Luigi Sapio, Alessia Salzillo, Angela Ragone, Michela Illiano, Annamaria Spina, Silvio Naviglio

Affiliations

  1. Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy.

PMID: 33126560 PMCID: PMC7693618 DOI: 10.3390/cancers12113166

Abstract

Intratumor heterogeneity (ITH) is considered the major disorienting factor in cancer treatment. As a result of stochastic genetic and epigenetic alterations, the appearance of a branched evolutionary shape confers tumor plasticity, causing relapse and unfavorable clinical prognosis. The growing evidence in cancer discovery presents to us "the great paradox" consisting of countless potential targets constantly discovered and a small number of candidates being effective in human patients. Among these, cyclic-AMP response element-binding protein (CREB) has been proposed as proto-oncogene supporting tumor initiation, progression and metastasis. Overexpression and hyperactivation of CREB are frequently observed in cancer, whereas genetic and pharmacological CREB downregulation affects proliferation and apoptosis. Notably, the present review is designed to investigate the feasibility of targeting CREB in cancer therapy. In particular, starting with the latest CREB evidence in cancer pathophysiology, we evaluate the advancement state of CREB inhibitor design, including the histone lysine demethylases JMJD3/UTX inhibitor GSKJ4 that we newly identified as a promising CREB modulator in leukemia cells. Moreover, an accurate analysis of strengths and weaknesses is also conducted to figure out whether CREB can actually represent a therapeutic candidate or just one of the innumerable preclinical cancer targets.

Keywords: CREB; GSKJ4; cancer therapy; drug inhibitors

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