Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with chemoresistance posing major treatment challenges. Here, we investigated the anticancer potential of pyrazolo[4,3-
e
]tetrazolo[1,5-
b
][1,2,4]triazine sulfonamides (MM129 and MM137) in combination with the ATM inhibitor KU-60,019 in HCT-116 and HT-29 CRC models. Combinatorial treatment significantly decreased cell viability, suppressed proliferation (BrdU and Ki-67), and increased neutral comet and γH2AX-associated DNA damage parameters compared to single-agent treatments. Cell death analyses showed mainly apoptosis-associated changes, while partial protection by NEC-1 suggests that additional non-apoptotic mechanisms may contribute under selected conditions. Our results indicate that MM compounds exhibit measurable anticancer activity in 3D spheroid models and that their combination with ATM inhibition modulates both viability and spheroid morphology, as reflected by changes in ATP levels, core size, and diffusion parameters. Further optimization and mechanistic studies are required to determine the extent and basis of any combinatorial benefit in this context.
M. Kciuk, Katarzyna Wanke, M. Mojzych et al.· Scientific Reports· 0 citations
The landscape of immunotherapy in oncology has markedly advanced with the development of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, fundamentally reshaping cancer treatment by potentiating anti-tumor immune responses. PD-1/PD-L1 blockade agents, such as FDA-approved nivolumab, pembrolizumab, and dostarlimab, have demonstrated significant clinical efficacy across various malignancies. Additionally, investigational agents like envafolimab, a novel PD-L1 inhibitor, are currently under clinical evaluation for efficacy and safety in solid tumors. This review examines the emerging data on envafolimab and discusses strategies to optimize its therapeutic impact, including combination regimens and personalized approaches. Tailoring treatments based on individual genetic, immunological, and microbiome profiles holds the potential to enhance response rates and the durability of outcomes. The integration of these factors is pivotal in advancing the precision and success of immunotherapy in oncology.
M. Kciuk, D. Kołat, Katarzyna Wanke et al.· Frontiers in Immunology· 0 citations
This review examines how stemness-associated signaling pathways, including Hedgehog, Notch, and Wnt/ β -catenin, interact with DDR programs to promote CSC survival under genotoxic stress, and summarizes current and emerging therapeutic strategies targeting CSC-specific DDR dependencies.
M. Kciuk, Julia Gałęziewska, Weronika Kruczkowska et al.· Oncology Research· 0 citations
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