TY - JOUR
T1 - Targeting CBP and p300: Emerging Anticancer Agents
AU - Masci, Domiziana
AU - Puxeddu, Michela
AU - Silvestri, Romano
AU - La Regina, Giuseppe
PY - 2024
Y1 - 2024
N2 - CBP and p300 are versatile transcriptional co-activators that play essential roles in regulating a wide range of signaling pathways, including Wnt/beta-catenin, p53, and HIF-1 alpha. These co-activators influence various cellular processes such as proliferation, differentiation, apoptosis, and response to hypoxia, making them pivotal in normal physiology and disease progression. The Wnt/beta-catenin signaling pathway, in particular, is crucial for cellular proliferation, differentiation, tissue homeostasis, and embryogenesis. Aberrant activation of this pathway is often associated with several types of cancer, such as colorectal tumor, prostate cancer, pancreatic and hepatocellular carcinomas. In recent years, significant efforts have been directed toward identifying and developing small molecules as novel anticancer agents capable of specifically inhibiting the interaction between beta-catenin and the transcriptional co-activators CBP and p300, which are required for Wnt target gene expression and are consequently involved in the regulation of tumor cell proliferation, migration, and invasion. This review summarizes the most significant and original research articles published from 2010 to date, found by means of a PubMed search, highlighting recent advancements in developing both specific and non-specific inhibitors of CBP/beta-catenin and p300/beta-catenin interactions. For a more comprehensive view, we have also explored the therapeutic potential of CBP/p300 bromodomain and histone acetyltransferase inhibitors in disrupting the transcriptional activation of genes involved in various signaling pathways related to cancer progression. By focusing on these therapeutic strategies, this review aims to offer a detailed overview of recent approaches in cancer treatment that selectively target CBP and p300, with particular emphasis on their roles in Wnt/beta-catenin-driven oncogenesis.
AB - CBP and p300 are versatile transcriptional co-activators that play essential roles in regulating a wide range of signaling pathways, including Wnt/beta-catenin, p53, and HIF-1 alpha. These co-activators influence various cellular processes such as proliferation, differentiation, apoptosis, and response to hypoxia, making them pivotal in normal physiology and disease progression. The Wnt/beta-catenin signaling pathway, in particular, is crucial for cellular proliferation, differentiation, tissue homeostasis, and embryogenesis. Aberrant activation of this pathway is often associated with several types of cancer, such as colorectal tumor, prostate cancer, pancreatic and hepatocellular carcinomas. In recent years, significant efforts have been directed toward identifying and developing small molecules as novel anticancer agents capable of specifically inhibiting the interaction between beta-catenin and the transcriptional co-activators CBP and p300, which are required for Wnt target gene expression and are consequently involved in the regulation of tumor cell proliferation, migration, and invasion. This review summarizes the most significant and original research articles published from 2010 to date, found by means of a PubMed search, highlighting recent advancements in developing both specific and non-specific inhibitors of CBP/beta-catenin and p300/beta-catenin interactions. For a more comprehensive view, we have also explored the therapeutic potential of CBP/p300 bromodomain and histone acetyltransferase inhibitors in disrupting the transcriptional activation of genes involved in various signaling pathways related to cancer progression. By focusing on these therapeutic strategies, this review aims to offer a detailed overview of recent approaches in cancer treatment that selectively target CBP and p300, with particular emphasis on their roles in Wnt/beta-catenin-driven oncogenesis.
KW - CBP
KW - Wnt/β-catenin pathway
KW - cancer
KW - small molecules
KW - inhibitors
KW - p300
KW - histone acetyltransferases
KW - CBP
KW - Wnt/β-catenin pathway
KW - cancer
KW - small molecules
KW - inhibitors
KW - p300
KW - histone acetyltransferases
UR - http://hdl.handle.net/10807/299038
UR - https://www.mdpi.com/1420-3049/29/19/4524
U2 - 10.3390/molecules29194524
DO - 10.3390/molecules29194524
M3 - Article
SN - 1420-3049
VL - 29
SP - 1
EP - 22
JO - Molecules
JF - Molecules
ER -