Clinical Cancer Drugs - Volume 5, Issue 2, 2018

Colorectal cancer (CRC) is the 3rd most common cause of cancer death worldwide. Regular screening of the asymptomatic population can drastically reduce the mortality rate. CRC screening includes several proceedings although the gold standard remains optical colonoscopy (OC), which is unpleasant, causes pain and discomfort. New technologies exemplified by capsule endoscopy (CE) constitute alternative painless solutions and despite their limitations, e.g., passive locomotion and absence of on-board instrumentation, are being increasingly used for CRC screening. Research and development centres are investigating novel advanced robotic technologies for diagnostic and therapeutic use. These include wireless communication, active locomotion, sensors, diagnostic, and therapeutic instruments. This review describes the traditional OC procedure and the existing robotic technologies for CRC.

Background: Endocrine Therapy (ET) is a mainstay in Hormone Receptor-positive Breast Cancer treatment. The ability to counter estrogenic signaling in mammary tissue has made Selective Estrogen Receptor Modulators, Aromatase Inhibitors and the Selective Estrogen Receptor Degrader fulvestrant essential therapies in both early and late stage settings, with good safety profiles and benefit/ risk ratios. Nonetheless, numerous tissues are affected by estrogen stimulation, and diverse adverse drug events have emerged. The Central Nervous System appears to be affected as well and claims of cognitive impairment following endocrine therapy have arisen. Objective: The study aimed to discuss the available evidences on the possible association of ET to cognitive impairment in breast cancer patients, gathering up-to-date information from clinical trials, meta-analysis, as well as expert opinions. Method: Appropriate and pertinent articles were retrieved through PubMed search. Results: Controversial data emerged from clinical trials as well as observational studies and metaanalysis. Many authors have shown that verbal memory is negatively affected by exposure to tamoxifen. Moreover, significant lower memory test scores in the aromatase inhibitor-treated patients have been reported. On the other hand, there are clinical and preclinical evidence suggesting that tamoxifen may have a protective role in the Central Nervous System. Conclusion: To date, the association between ET and cognitive impairment has not yet been proven. Future studies on available and upcoming drugs will need to include proper cognitive evaluation scales and an adequate number of participants in order to better define the role of ET in the possible development of cognitive impairment in breast cancer patients.

Background: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cause of death worldwide with the majority of patients presenting with advanced disease at the time of diagnosis. Objective: In this review, the emergence of erlotinib as a seed for the treatment of NSCLC has been discussed and how it is gaining limelight as one of the most suitable drugs for this indication. The approval status in different regions and recommendation data from Health Technology Assessment (HTA) agencies like National Institute for Care and Excellence (NICE), UK and Wales and Scottish Medical Consortium (SMC), Scotland have also been collected in this study. Method: For carrying out the review, literature was searched on various databases including PubMed, Clinicaltrial.gov, various HTA databases, EMBASE, Google Scholar, United States Food and Drugs Administration (USFDA) and various other online databases. Information from these sources was compared and analyzed as per the requirement of the objective. Results: From the literature obtained after searching various databases, it was observed that Erlotinib (Tarceva) is one of the drugs which acts on EGFR and was approved (2004) from USFDA for treating locally advanced or metastatic NSCLC, as second or third line treatment after the failure of chemotherapy regimen. Different Health Technology Assessment (HTA) agencies have also assessed erlotinib for various indications and have given guidance for its use. Conclusion: On the basis of available literature and data on clinical studies, it can be concluded that erlotinib can be the better option for treatment of NSCLC and effective against different lines of treatment and in maintenance as well.

Background: Tumor Necrosis Factor (TNF) is a significant cytokine produced by activated monocytes/macrophages that exhibit selective cytotoxicity against various tumor cells. It has attracted attention as a potential antitumor agent through the regulation of cell proliferation, differentiation, and apoptosis. Need: Chemotherapeutic agents lack target specificity while TNF specifically attacks malignant cells through the Tumor Necrosis Factor Receptor (TNFR). TNF showed severe side effects in phase I & phase II clinical trials which restrict its dosage to such an extent that no persistent anti-cancer effect has been seen. Thus, TNF has a limited role in treating human cancer unless its side effects are minimized. Formerly, no researcher has designed molecules targeting TNFR. In order to design novel chemical entities, active binding site of the receptor must be known. Objective: The study aimed to predict the active binding site of TNFR1 using molecular modeling approach and further designing of novel peptides targeting TNFR1. Method: Various in silico studies were performed to predict and validate the active binding site of TNFR1. Results: The present in silico study of TNF β-TNFR1 complex predicts the active binding site of TNFR1 and the same was validated. Drug repurposing approach was used to define the need for designing anticancer molecules targeting TNFR1. Novel peptides were designed that target the active binding site of TNFR1. This study may open up the new avenues towards the designing of novel potential anticancer molecules targeting TNFR1. Conclusion: This study has implications in the rational designing of novel chemical entities that target and modulate TNFR.

Objective: In the present study, the utilization of a novel biocompatible and biodegradable Methotrexate controlled release injectable formulation is established. The drug delivery vehicle used is an autogelling pH sensitive formulation, which is based on the natural biopolymer chitosan. Methods: Chitosan/glyceryl monooleate (C/GMO) solution was prepared in 0.33 M citric acid with gentle stirring. The weighed quantity of Drug and Chitosan in the required concentration was stirred with an appropriate quantity of 0.33 M Citric acid for 3 hours. Further, this solution was cooled to 4oC. Then, to this cooled Chitosan and Drug solution, the desired amount of Glycerol Monooleate was added dropwise with constant stirring to obtain a clear homogenous system. Moreover, it was filtered by membrane filtration using the cellulose membrane. Finally, the prepared pH sensitive formulations were sterilized by autoclaving. Results: The drug release of the final formulation as cumulative percent drug release was found out to be 80.93%, 95.78%, 75.86%, 93.58% and 84.10% for formulation F1, F2, F3, F4 and F5 respectively after 8 hours. The in vitro drug release study had shown that the formulation F2 had better-sustained effect than other existing pH-induced formulations. Conclusion: All these findings showed that chitosan/GMO gel was found to be safe, effective, homogeneous and stable injectable formulation for sustained delivery of Methotrexate and presented an approach for the striking technology offering the platform for the delivery of other clinically significant anticancer drugs.

Objectives: Investigation of effects of lysozyme (glycoside hydrolase) on Ehrlich ascites carcinoma cells. Studies of influence of these effects on the physiological fate of cells. In particular investigations of possible apoptosis inducing effects of the enzyme by annexin V binding assay. Materials and Methods: Annexin V binding assay was applied for the detection of changes in plasma membrane of Ehrlich carcinoma cells as a result of lysozyme action. In particular, FITC-Annexin V and silver nanoparticles-Annexin V conjugates were used for the detection of these changes. Results: It was demonstrated that as a result of the enzyme action Ehrlich carcinoma cells acquire annexin V binding ability. It means that drastic changes in plasma membranes take place that can be the hallmark of apoptosis. Further, we have developed a new approach for annexin V binding assay by application of anisotropic silver nanoparticles sensitized with annexin V. Conclusion: It is shown that lysozyme brings drastic changes in plasma membrane of Ehrlich carcinoma cells. As a result of its action, these cells acquire annexin V binding ability - hallmark of early stage of apoptosis. For the first time silver nanoparticles sensitized with annexin V were applied to study membrane dynamics.