Targets, Volume 2, Issue 3 (September 2024) – 6 articles

Drug resistance in cancer is a significant contributor to high mortality, and it exists in the complex form of a multi-parameter. Here, we unravel the roles of tumor heterogeneity, intratumoral physiological barriers, and safe havens in the onset and progression of cancer drug resistance, and outline strategies for resolution. We advocate for a “three-step approach” to reverse cancer drug resistance, including the management of cancer evolution and early intervention, the normalization of intratumoral physiological barriers, and the breakage of tumor safe havens. This approach aims to effectively manage the source of drug resistance, dismantle the breeding grounds of drug resistance, and break the sanctuaries where drug resistance hides. Full article

The vast majority of advanced NSCLC cases are histologically represented by adenocarcinomas. EGFR activating mutations (exon 19 deletions, exon 21 L858R substitutions, exon 20 insertions) represent one of the most common druggable alterations. Since erlotinib’s FDA approval in 2013, EGFR-TKIs have represented a staple of EGFR+ advanced NSCLC treatment, with osimertinib representing the latest major FDA-approved third-generation EGFR-TKI. In recent years, however, several preclinical data have highlighted promising results regarding combination therapies involving EGFR-TKIs plus chemotherapy, and various recent clinical trials have confirmed these results. In addition, in 2021, amivantamab was the first FDA-approved mAb for the treatment of EGFR+ advanced NSCLC patients; according to some extremely up-to-date clinical trials, the combination of amivantamab plus chemotherapy is also associated with superior results. Therefore, this paper aims to provide a comprehensive review of both the bases and the latest evidence of the combination therapies involving EGFR+ advanced NSCLC patients. Full article

Epigenetic modulation of DNA and histones facilitated by and histone deacetylases (HDAC) is associated with the development and progression of many cancers, although less is known about DNA methyltransferase (DNMT) in oral cancers and the regulation of these targets. Using commercially available cell lines, oral squamous cell carcinomas (SCC4, SCC9, SCC15, SCC25, and CAL27), and normal gingival fibroblasts (HGF-1), growth assays and mRNA expression were evaluated using ANOVA. These results revealed homeostasis enzyme DNMT1 expression was significantly higher among slow-growing HGF-1 cells than among fast-growing oral cancers, p < 0.05. In contrast, DNMT3A and DNMT3B expression was significantly higher among oral cancers compared with HGF-1 cells, p < 0.05. However, differential expression of HDAC1 and HDAC2 was observed among SCC4, SCC25, and CAL27 cells. Further analysis of miR-152 (regulation and control of DNMT expression) and miR-21, miR-221, and miR-145 (regulation of HDAC expression) revealed all oral cancers produced miR-21, but none produced miR-221. However, differential expression of miR-145 (SCC15) and miR-152 (SCC25) suggested alternative epigenetic pathways and mechanisms of DNMT and HDAC regulation may be responsible for some of the observations revealed in this study. Full article

The significance of hydrogen sulfide (H₂S) in biological research is covered in detail in this work. H₂S is a crucial gas-signaling molecule that is involved in a wide range of illnesses and biological processes. Whether H₂S has a beneficial therapeutic effect or negative pathological toxicity in an organism depends on changes in its concentration. A novel approach to treatment is the regulation of H₂S production by medications or other measures. Furthermore, H₂S is a useful marker for disease assessment because of its dual nature and sensitivity. We can better understand the onset and progression of disease by developing probes to track changes in H₂S concentration based on the nucleophilicity, reducing properties, and metal coordination properties of H₂S. This will aid in diagnosis and treatment. These results demonstrate the enormous potential of H₂S in the detection and management of disease. Future studies should concentrate on clarifying the relationship between diseases and the mechanism of action of H₂S in organisms. Ultimately, this work opens new possibilities for disease diagnosis and treatment while highlighting the significance of H₂S in biological research. Future clinical practice and medical advancements will benefit greatly from our thorough understanding of the mechanism of action and therapeutic applications of H₂S. Full article

The landscape of cancer therapy has gained major impetus through the development of materials capable of selectively targeting cancer cells while sparing normal cells. Synthetic peptides are appealing as scaffolds for the creation of such materials. They are small in size, amenable to chemical synthesis and functionalization, and possess diverse chemical and structural space for modulating targeting properties. Here, we review some fundamental insights into the design, discovery, and evolution of peptide-based targeting agents, with a particular focus on two types of cancer cell targets: unique/overexpressed surface receptors and abnormal physiological properties. We highlight the cutting-edge strategies from the literature of the last two decades that demonstrate innovative approaches to constructing receptor-specific cyclic binders and stimulus-responsive targeting materials. Additionally, we discuss potential future directions for advancing this field, with the aim of pushing the frontiers of targeted cancer therapy forward. Full article

Facing the increasingly global crisis of antibiotic resistance, it is urgent to develop new antibacterial agents and methods. Simultaneously, as research progresses, the occurrence, development, and treatment of diseases, especially some malignant cancers, are found to be closely associated with the bacterial microenvironment, prompting us to reconsider the efficiency of existing antibacterial strategies for disease treatments. Bacteriophages have been employed as antibacterial agents for an extended period owing to their high biocompatibility and particular targetability toward the host bacterial strains. Nonetheless, they are almost neglected due to their slow and limited efficacy in antibacterial practice, especially in acute and severe infectious cases. In recent years, fantastic advancements in various biochemical technologies, such as bacteriophage display technology, genetic engineering, and chemical molecular engineering, have enabled scientists to conduct a broader range of modifications and transformations on the existing bacteriophages with inherited unique characteristics of themselves. As a result, a series of novel bacteriophage platforms are designed and fabricated with significantly enhanced properties and multiplied functionalities. These offer new avenues for combating infections caused by drug-resistant bacteria and treatment of malignancies that are associated with bacterial infections, holding great significance and potential in the innovative theranostic applications. Full article