Current Cancer Therapy Reviews - Volume 18, Issue 2, 2022

This review article gives a brief account of advances in the treatment of cancer via nanodelivery systems. We have discussed benefits of different nanocarriers that have the potential to deal with the problem of non-selectivity of conventional anticancer drugs. Targeted drug delivery not only spares healthy cells from harmful effects of anticancer drugs but also reduces the amount of drug to be administered; various drug delivery systems have been fabricated using appropriate nanocarriers. In fact, some carrier systems are biodegradable and degrade in the body into nontoxic moieties, thereby adding safety characteristics to the formulation. Selectivity towards cancer cells makes nanodelivery system a choice for the treatment of cancer as compared to conventional drug delivery. This review discusses various targeting strategies, different nanodelivery systems, characteristics required to be an ideal drug delivery system, advantages of these systems, and future prospects of such systems.

New therapies and alternatives for the containment of tumor progression are being proposed for the treatment of cancer. In this context, monoclonal therapies using Immune Checkpoint Inhibitors (ICI) come as a therapeutic proposal. They are responsible for immunological control by blocking PD-1, PD-L1 and CTLA-4 molecules. However, among the effects caused by therapy, the use of medications is associated with neurological diseases reported as an adverse effect, affecting the Central Nervous System (CNS) and causing a wide range of symptoms. In this regard, the present bibliographic review presents the main CNS disorders associated with this therapy, in addition to the incidence, symptoms and treatment of these diseases.

Triazole is the main five-membered Nitrogen-containing basic heterocyclic ring system reported for their biological activities and compounds with multiple pharmacophores, which fetch together acquaintance of a target with sympathetic types of the molecule that might interact with the target. In addition, healthy, adaptable, and scalable chemistry must be employed to achieve the task. This characteristic feature of triazole would make a good template for a lead cohort library. The current review article focuses on recent advancements in triazole moiety as an anti-cancer agent with their mechanism pathways of synthesized analogues.

Background: Melanoma, also known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin but may rarely occur in the mouth, intestines or, eye. This study aims to examine the expression of the mammalian target of rapamycin (mTOR)/70S6K signaling pathway in melanoma cancer. Methods: The B16F10 cell line treated with dacarbazine IC50 and different concentrations of metformin (0.5, 2, and 8 mM) for 24 hr and mTOR and 70S6k proteins expression were examined by western blotting. Cell viability was measured by MTT assay. Results: Western blot analysis showed that after different concentrations of metformin and dacarbazine treatments, the mTOR and 70S6K protein expression significantly (P<0.05) decreased. Conclusion: Metformin-induced repression of mTOR/70S6k axis activity disrupts B16F10 growth. Thus, we believe that combination therapy may be a suitable potential therapeutic target for melanoma cancer.

Background: Lung cancer can be treated with surgery, chemotherapy, radiation therapy, targeted therapy, and palliative care. Palliative therapy is applied for inoperable lung cancer as it induces tumour necrosis. PH of tumour tissue is acidic; application of sodium bicarbonate (SB) into lung cancer locally via bronchoscopy can change its core pH, which may lead to tumour destruction. We aimed to study the ultrastructural characteristics of lung cancer and assess the destructive effects of sodium bicarbonate 8.4% local injection on tumour tissue integrity by light and electron microscopies. Methods: This study was conducted on 21 patients with central bronchial carcinoma diagnosed according to WHO classification 2015. Three bronchoscopic biopsies were taken; two biopsies before and one after injection of sodium bicarbonate 8.4% solution of 20 ml via transbronchial needle. All biopsies were examined by both light and electron microscopes. The first biopsy was examined to diagnose the tumour morphologically with and without immunostaining. Second and third biopsies were taken before and after SB 8.4% injection to compare pathological changes in tumour tissue integrity as well as cellular ultra-structures. Different lung cancer pathological types were included in the study. Results: Tumour tissue integrity and pathological changes were examined in biopsies before and after injection of sodium bicarbonate 8.4%. Extensive necrosis in all cell types of lung cancer was seen after injection of SB; this important finding was delineated by both light and electron microscopies. Conclusion: Preliminary ultrastructural study of small biopsy of lung tumors has a complementary role in both morphological and immunohistochemical studies. Local injection of sodium bicarbonate into lung cancer induces extensive necrosis that may reflect its important therapeutic role in lung cancer.

Background: Several computer-aided drug design (CADD) methods enable the design and development of novel chemical entities. Structure-based drug design (SBDD) and the knowledge of in silico methods enable the visualization of the binding process of ligands to targets and to predict the key binding pocket sites and affinity of ligands to their target macromolecules. Objective: The present study was carried out to identify novel N-2-amino-N-phenyl quinoline-3- carboxamide (AQCMs) derivatives targeting Platelet-derived growth factor receptor (PDGFR) to cure cancer using in silico approach. Materials and Methods: AQCMs were designed using ChemAxon Marvin Sketch 5.11.5 software. SwissADME and admetSAR online webserver were used to predict physicochemical properties as well as the toxicity of compounds. Ligand-receptor interactions between quinoline-3-carboxamide derivatives with the target receptor (PDB: 5GRN) were carried out using molecular docking technique by employing various software like AutoDock 1.1.2, MGL Tools 1.5.6, Discovery Studio Visualizer v 20.1.0.19295, Procheck, ProtParam tool, and PyMOL. Results: In silico results reveal that all designed compounds had acceptable pharmacokinetic properties, were found to be orally bioavailable, and less harmful. Molecules from 36 to 39 showed better docking scores as compared to standard drugs sunitinib and tasquinimod. Conclusion: Increase in binding energy and the number of H-bonds established by AQCMs with below 3.40 Å distance interactions allows a valuable starting point in order to optimize compounds for further investigation. Pharmacokinetics and toxicological profile build up the applicability of quinoline-3-carboxamide moiety as a potential new candidate for the cure of cancer that could help the medicinal chemists for additional extensive in vitro, in vivo chemical, and pharmacological investigations.

Introduction: In women, breast cancer is a prevalent malignancy. One of the important genes in breast cancer progression is Pinin. LncRNAs H19 plays an important role in breast cancer cell development. In this study, the correlation between a miRNA-related rs532 polymorphism (G) and the level of expression of Pinin and lncRNA H19 in breast cancer tissues was investigated. Methods: Tissue samples were collected from 64 patients with breast cancer. RT-PCR with highresolution melting (HRM) analysis was used. Results: Our data suggest that there is significant up-regulation in the expression of lncRNA H19 and the Pinin gene in breast cancer tissue compared to the control ones. The Pinin polymorphism rs532 G is significantly associated with Pinin expression of breast cancer tissue compared to the control one. Discussion: The rs532 G polymorphism is located around the pinin and its allele frequency is significantly associated with Pinin expression. Perhaps, rs532 G polymorphism could be functional in breast cancer progression through the impact on pinin expression. There is no correlation between SNP and lncRNA H19. Conclusion: The polymorphism rs532 G polymorphism is significantly associated with Pinin expression of breast cancer tissue from Isfahan patients which suggests the miRNA-141has potential to regulate Pinin expression levels.

Background: Hepatocellular carcinoma (HCC) is the most prevalent kind of primary liver cancer and a significant cause of cancer-related mortality across the world. Sorafenib is considered the approved drug of choice in advanced HCC, which is an oral multikinase inhibitor with effective antiproliferative and antiangiogenic effects. In India, there is currently insufficient data on the safety and efficacy of sorafenib in the treatment of HCC. Objective: The study aims to evaluate the safety and effectiveness of sorafenib therapy in advanced HCC. Methods: A prospective study of 66 patients administered with sorafenib for advanced HCC between June 2016 and May 2017 was carried out in a single center with a mean follow-up of 3 months. The adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Effectiveness was analyzed based on alpha-fetoprotein (AFP) levels from laboratory findings. The median age was 63 years (range 61-70), with the male to female ratio of 16:1. Results: The most commonly observed adverse events were fatigue (31.81%), hand-foot syndrome (24.24%), and diarrhea (24.24%). A statistically significant decline in AFP levels was observed with sorafenib treatment (p= <0.001). Conclusion: Sorafenib appears to be beneficial for individuals with advanced HCC, regardless of the baseline condition.

Background: Cancer is one of the leading chronic diseases with a high mortality rate worldwide. Current statistical studies on cancer from the World Health Organization (WHO) in 2020 estimated that cancer is the first or second leading cause of death. Objective: The current study investigated the phytochemical, antioxidant, and anticancer effect of MeOH extract of Morus alba leaves, superoxide scavenging assay, metal chelating, DPPH, and MTT assay employed. Methods: MTT assay was performed on A549 cells and chick embryo fibroblasts were used as the control. DNA fragmentation and real-time assays were performed to check apoptosis and gene expression levels. Results: Findings suggest that the MeOH extract of Morus alba exhibited a significant antioxidant activity compared to standard antioxidants. MeOH extract and chloroform fraction exhibited strong selectivity of toxicity toward A549 human lung carcinoma cells without affecting normal cells. The chloroform fraction was found to be most active in the MTT assay against A549 cells, while it was less toxic to normal cells. Cells exposed to IC50 concentration for the cytotoxicity study of the chloroform fraction exhibited a breakdown of DNA. Increased expression of p53, Bax, caspase-3 and reduced expression of Bcl-2 gene gave evidence that the chloroform fraction might induce apoptosis. Conclusion: It was concluded that the MeOH extract and its fractions of Morus alba leaves possessed immense potential for tumor treatment. Therefore, it would be necessary to carry out further studies to isolate and identify the active principles responsible for these activities.