Advances in Oligonucleotide Aptamers for NSCLC Targeting.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, with the highest incidence in developed countries. NSCLC patients often face resistance to currently available therapies, accounting for frequent relapses and poor prognosis. Indeed, despite great recent advancements in the field of NSCLC diagnosis and multimodal therapy, most patients are diagnosed at advanced metastatic stage, with a very low overall survival. Thus, the identification of new effective diagnostic and therapeutic options for NSCLC patients is a crucial challenge in oncology. A promising class of targeting molecules is represented by nucleic-acid aptamers, short single-stranded oligonucleotides that upon folding in particular three dimensional (3D) structures, serve as high affinity ligands towards disease-associated proteins. They are produced in vitro by SELEX (systematic evolution of ligands by exponential enrichment), a combinatorial chemistry procedure, representing an important tool for novel targetable biomarker discovery of both diagnostic and therapeutic interest. Aptamer-based approaches are promising options for NSCLC early diagnosis and targeted therapy and may overcome the key obstacles of currently used therapeutic modalities, such as the high toxicity and patients' resistance. In this review, we highlight the most important applications of SELEX technology and aptamers for NSCLC handling.

Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors.

The EphA2 receptor tyrosine kinase is overexpressed in most solid tumors and acts as the major driver of tumorigenesis. In this study, we developed a novel approach for targeting the EphA2 receptor using a 2'-fluoro-modified pyrimidine RNA aptamer termed ATOP. We identified the ATOP EphA2 aptamer using a novel bioinformatics strategy that compared aptamers enriched during a protein SELEX using recombinant human EphA2 and a cell-internalization SELEX using EphA2-expressing MDA231 tumor cells. When applied to EphA2-expressing tumor cell lines, the ATOP EphA2 aptamer attenuated tumor cell migration and clonogenicity. In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.

Epigenetic regulation of adipogenesis by histone-modifying enzymes.

Many studies investigating the transcriptional control of adipogenesis have been published so far; recently the research is focusing on the role of epigenetic mechanisms in regulating the process of adipocyte development. Histone-modifying enzymes and the histone tails post-transcriptional modifications catalyzed by them, are fundamentally involved in the epigenetic regulation of adipogenesis. In our review, we will discuss recent advances in epigenomic regulation of adipogenesis with a focus on histone-modifying enzymes implicated in the various phases of adipocytes differentiation process from mesenchymal stem cells to mature adipocytes. Understanding adipogenesis, may provide new ways to treat obesity and related metabolic diseases.

Emerging Therapeutic RNAs for the Targeting of Cancer Associated Fibroblasts.

Tumor mass consists of a complex ensemble of malignant cancer cells and a wide variety of resident and infiltrating cells, secreted factors, and extracellular matrix proteins that are referred as tumor microenvironment (TME). Cancer associated fibroblasts (CAFs) are key TME components that support tumor growth, generating a physical barrier against drugs and immune infiltration, and contributing to regulate malignant progression. Thus, it is largely accepted that therapeutic approaches aimed at hampering the interactions between tumor cells and CAFs can enhance the effectiveness of anti-cancer treatments. In this view, nucleic acid therapeutics have emerged as promising molecules. Here, we summarize recent knowledge about their role in the regulation of CAF transformation and tumor-promoting functions, highlighting their therapeutic utility and challenges.