• Bulletin of the Korean Chemical Society
• /
• 제30권8호
• /
• pp.1827-1831
• /
• 2009

Ligand molecules that can recognize and interact with cancer cell surface marker proteins with high affinity and specificity should greatly aid the development of novel cancer diagnostics and therapeutics. HER-2/ErbB2/Neu (HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves as both a useful biomarker and a therapeutic target for breast cancer. In this study, we aimed to isolate RNA aptamers that specifically bind to a HER-2-overexpressing human breast cancer cell line, SK-BR-3, using Cell-SELEX strategy. The selected aptamers showed strong affinity to SK-BR-3, but not to MDAMB- 231, a HER-2-underexpressing breast cancer cell line. In addition, we confirmed the specific targeting of HER-2 receptor by aptamers using an unrelated mouse cell line overexpressing human HER-2 receptor. The HER-2-targeting RNA aptamers could become a useful reagent for the development of breast cancer diagnostics and therapeutics.

• BMB Reports
• /
• 제57권9호
• /
• pp.388-399
• /
• 2024

Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors.

• Biomolecules & Therapeutics
• /
• 제21권2호
• /
• pp.89-96
• /
• 2013

Atherosclerotic vascular dysfunction is a chronic inflammatory process that spreads from the fatty streak and foam cells through lesion progression. Therefore, its early diagnosis and prevention is unfeasible. Reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerotic vascular disease. Intracellular redox status is tightly regulated by oxidant and antioxidant systems. Imbalance in these systems causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, and leads to dysregulation. Paradoxically, large clinical trials have shown that non-specific ROS scavenging by antioxidant vitamins is ineffective or sometimes harmful. ROS production can be locally regulated by cellular antioxidant enzymes, such as superoxide dismutases, catalase, glutathione peroxidases and peroxiredoxins. Therapeutic approach targeting these antioxidant enzymes might prove beneficial for prevention of ROS-related atherosclerotic vascular disease. Conversely, the development of specific antioxidant enzyme-mimetics could contribute to the clinical effectiveness.

• BMB Reports
• /
• 제48권4호
• /
• pp.234-237
• /
• 2015

Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

• Biomolecules & Therapeutics
• /
• 제21권5호
• /
• pp.323-331
• /
• 2013

TGF-${\beta}$ pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-${\beta}$ related functional contexts. This review discusses the molecular mechanism of the TGF-${\beta}$ pathway and describes the different ways of tumor suppression and promotion by TGF-${\beta}$. In the last part of the review, the data on targeting TGF-${\beta}$ pathway for cancer treatment is assessed. The TGF-${\beta}$ inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

• Biomolecules & Therapeutics
• /
• 제26권1호
• /
• pp.19-28
• /
• 2018

Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.

• Clinical and Experimental Pediatrics
• /
• 제54권6호
• /
• pp.241-245
• /
• 2011

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in several organs, including subependymal giant cell tumors. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2-encoded proteins modulate cell function via the mammalian target of rapamycin (mTOR) signaling cascade, and are key factors in the regulation of cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. The mTOR pathway represents a logical candidate for drug targeting, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.

• BMB Reports
• /
• 제46권7호
• /
• pp.338-345
• /
• 2013

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from defects in several gene sets; therefore, disease progression could be prevented using miRNAs targeting multiple genes. Moreover, recent studies suggest that miRNAs reflect the stage of the specific disease, such as carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic liver disease, pancreatic cystic disease, and ovarian cystic disease, have common processes of cyst formation in the specific organ. Specifically, epithelial cells initiate abnormal cell proliferation and apoptosis as a result of alterations to key genes. Cysts are caused by fluid accumulation in the lumen. However, the molecular mechanisms underlying cyst formation and progression remain unclear. This review aims to introduce the key miRNAs related to cyst formation, and we suggest that miRNAs could be useful biomarkers and potential therapeutic targets in several cystic diseases.

• Molecules and Cells
• /
• 제41권6호
• /
• pp.506-514
• /
• 2018

The transcriptional regulation of genes determines the fate of animal cell differentiation and subsequent organ development. With the recent progress in genome-wide technologies, the genomic landscapes of enhancers have been broadly explored in mammalian genomes, which led to the discovery of novel specific subsets of enhancers, termed super-enhancers. Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases. Here, I provide a comprehensive description of the optimal approach for identifying functional units of super-enhancers and their unique chromatin features in normal development and in diseases, including cancers. I also review the recent updated knowledge on novel approaches of targeting super-enhancers for the treatment of specific diseases, such as small-molecule inhibitors and potential gene therapy. This review will provide perspectives on using super-enhancers as biomarkers to develop novel disease diagnostic tools and establish new directions in clinical therapeutic strategies.

• Journal of Industrial and Engineering Chemistry
• /
• 제67권
• /
• pp.429-436
• /
• 2018

Targeted intracellular delivery of therapeutic agents is one of the great challenges for cancer treatment. Aptamers that bind to a variety of biological targets have emerged as new targeting moieties with high specificity for targeted cancer therapy. In this study, near-infrared (NIR) light-absorbing hollow gold nanocages (AuNCs) were synthesized and conjugated with AS1411 aptamer to achieve cancer-targeted photothermal therapy. AuNC functionalized with PEG and AS1411 (AS1411-PEG-AuNC) exhibited selective cellular uptake in breast cancer cells due to selective binding of AS1411 to nucleolin, a protein that is over-expressed in cancer cells over normal cells. As a result, AS1411-PEG-AuNC showed cancer-targeted photothermal activity. This study demonstrates that aptamer-conjugated AuNCs are effective tumor-targeting photothermal agents.