Epigenetic modifications play a crucial role in cancer, influencing cellular physiology, extracellular matrix (ECM) remodeling, and immune responses. With growing emphasis on chromatin remodeling and the epigenetic regulation of immunity, these regulatory pathways and related players have become focal points of oncological investigations. Epigenetic manipulation of immune system components has emerged as a promising strategy in cancer treatment. Several FDA-approved "epi-drugs" target the epigenome to modulate immune responses and offer new opportunities across different cancers. DNA repair pathways contribute significantly to the avoidance of cancer initiation and also contribute to cellular resistance in cancer treatment. Chromatin remodelers such as INO80, Fun30, and RAD54 play essential roles in DNA damage response (DDR) through homologous recombination and non-homologous end-joining pathways, and their dysregulation leads to genome instability and tumor progression. Chromatin remodeling complexes, including SWI/SNF and CHD families, are frequently altered across various cancer types, further highlighting their role in cancer pathophysiology. Targeting these chromatin modifiers and associated DNA repair mechanisms may provide novel therapeutic options. In addition, combining epigenetic modulators with immunotherapies has shown promise in enhancing responses to immune checkpoint blockade. Epigenetic drugs such as histone deacetylase (HDAC) inhibitors and DNA methylation inhibitors are being explored for their synergistic effects with immunotherapy. While the interplay between chromatin remodeling, DNA repair, and immune responses provides a strong framework for developing targeted oncological strategies, further research is required to better understand these interactions and optimize their clinical application.
S. Riaz, Mehwish Iqbal, Farwa Tahir et al.· Molecular Medicine· 0 citations
Phytophthora infestans, the causal agent of late blight in potato and tomato, is a historically devastating pathogen that continues to pose a major threat to global food security. Although conventional fungicides remain a cornerstone of crop protection, growing concerns over their environmental impact and long-term sustainability have driven the search for safer and more selective alternatives. In this context, next-generation fungicides with high specificity and minimal ecological footprint are urgently needed. This study introduces CP32, a small cyclic peptide, identified via yeast two-hybrid screening of a genetically encoded combinatorial peptide library, based on its specific interaction with the catalytic domain of the P. infestans enzyme Cellulose Synthase 2. CP32 exhibits anti-oomycete activity, effectively inhibits sporangial growth at low micromolar concentrations, and significantly reduces late blight symptoms on tomato leaves and entire plants. In silico docking analyses, supported by molecular and biochemical evidence, confirm that CP32 compromises cell-wall integrity by interfering with cellulose deposition and altering glucan composition. Furthermore, CP32 readily permeates the Phytophthora membrane and displays oomycete-static properties, while showing no detectable toxicity toward non-target organisms, such as bacteria, yeast, or plants. Collectively, these findings identify CP32 as a promising, targeted anti-oomycete agent with a unique mode of action, targeting the P. infestans cell wall, representing a valuable contribution to the development of sustainable strategies for the control of late blight.
Demetrio Marcianò, S. Rosa, Elena Marone Fassolo et al.· Journal of Integrative Plant...· 0 citations
