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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Oncogenes are homologs of normal genes that typically have a role in cell cycle regulation and cell growth pathways. A mutation in an oncogene may result in consecutive activation of that gene, leading to uncontrolled cellular proliferation [13]. Among the oncogenes, the RAS oncogene is implicated in cancer development. This oncogene exists in three variants on the cellular level, HRAS, KRAS, and NRAS. When mutated, all these three oncogenes are able to transform normal cells into cancer cells. However, in colorectal cancer, KRAS is the most frequently mutated [14, 15].
Nanotechnology in Preventive and Emergency Healthcare
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Nilutpal Sharma Bora, Bhaskar Mazumder, Manash Pratim Pathak, Kumud Joshi, Pronobesh Chattopadhyay
The applications of nanomedicine in the field of respiratory diseases include drug delivery, hyperthermia, diagnostics, and gene therapy. Due to their size, nanomaterials have the capacity to reach almost any tissue, and the advantage of nanoparticle binding with drug molecules via linker compounds or encapsulation makes them a clear winner when it comes to the treatment of diseases involving the pulmonary system. For example, in the case of pulmonary tumors, the leaky vasculature of the tumor tissues can serve as an advantage to achieve passive targeting of chemotherapeutic-loaded nanoparticles (Hobbs et al., 1998). Pulmonary nanomedicine mostly utilizes this advantage of leaky vasculature, which is also known as the enhanced permeability and retention (EPR) effect, to exert its action. Genoxol-PM, a first-generation type respiratory nanomedicine comprised of a polymeric paclitaxel-loaded poly(lactic acid)-block PEG micelle-formulation, has been tested through phase II trials in patients with advanced non-small cell lung cancer (NSCLC). The response rate was found to be 46.5%, with a lower incidence of emetogenicity. However, adverse events like neutropenia and pneumonia were observed (Ahn et al., 2014; Sanna et al., 2014). Nano-DDS possessing ligands that target specific sites form the second-generation type of respiratory nanomedicine. The ligands can be aptamers, antibodies, proteins, or small molecules. Tumor specific mAb with active targeting capacity are already widely used in cancer therapy. Polyglycolic acid nanoparticles conjugated with cetuximab antibodies for targeting and loaded with the drug paclitaxel palmitate significantly increased the survival rate of mice with A549-luc-C8 lung tumors when compared with the control group (Karra et al., 2013). Aptamers (synthetic oligonucleotides) are another approach by which specific drug targeting can be achieved. Their advantages include specificity, small size, and lack of immunogenicity. Most tumors express a high density of folate and protein receptors. Since folate is a small molecule, it can be effectively used as a ligand in order to achieve drug targeting. Also, the overexpression of protein receptors can be exploited to achieve specific drug targeting by the use of transferrin and similar proteins as ligands in nanomedicine (Libutti et al., 2010). Numerous nanomedicines are already being used clinically for the treatment of lung cancer, like nanocarriers with Aurimmune Cyt-6091 and Bind-014. The former, Aurimmune Cyt-6091, has been used against adenocarcinoma of the lung in a phase I clinical trial (with future plans for phase II trials), and is a DDS based on AuNPs functionalized with PEG and tumor necrosis factor alpha (TNF-α), with TNF-α acting as both a targeting and therapeutic agent. The later, Bind-014, is composed of a PLA core, within which docetaxel is physically entrapped, and is under phase II trials for the treatment of NSCLC. It has been observed that Bind-014 is well tolerated, active, and exerts fewer side effects when compared to solvent-based docetaxel. It has also demonstrated marked effects on patients with KRAS mutations, where ordinary antitumor drugs fail to exert any effects (Biosciences, 2013; Hrkach et al., 2012; Libutti et al., 2010; Natale et al., 2014; Omlor et al., 2015).
Relevance of mouse lung tumors to human risk assessment
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Samuel M. Cohen, Yan Zhongyu, James S. Bus
Increasingly there have been investigations of the molecular changes occurring in lung tumors and comparing the alterations in human adenocarcinomas to those observed in experimental animal models especially in mice since these might be readily manipulated genetically (Nikitin et al. 2004; Pandiri et al. 2012). For example, KRAS is frequently mutated in lung adenocarcinomas in humans and mice. Further, transcriptomic analyses of human adenocarcinomas and those in mice demonstrated considerable similarities in the canonical pathways that are affected, including the eIF2 and mTOR pathways that might be activated by various stressors such as heat shock, hypoxia, and nutritional deficiencies, pathways involved in immune response and in xenobiotic metabolism amongst others. However, such alterations are common to many tumors and are more characteristic of cancer in general than specific to adenocarcinoma. Further, the molecular changes are similar regardless of the causation. The molecular changes in the tumors do not address the mode of action leading to the formation of the malignancy, but rather they are characteristics of the malignancies themselves. For example, lung carcinomas in human cigarette smokers and in never smokers are similar morphologically, molecularly, and in metastatic behavior.