Topics in Anti-Cancer Research

The development of the new sequencing technologies has unveiled a new world of regulatory non-coding RNAs (ncRNAs) that is revolutionizing our understanding of the RNA world. New transcripts with non-coding functions are being identified from most of the human genome. Although we have just started to study these ncRNAs, the broad list of regulatory functions assigned to them has assured a prominent role in the regulation of the molecular processes involved in human cancer. This chapter presents a review of the state of the art in the study of ncRNAs and their relationship with human cancer, summarizing the origin, structure and function of the most relevant new classes of ncRNAs. In addition, a selection of recent patents related to ncRNAs and human cancer is included here, analyzing their promising potential in the diagnosis and treatment of human cancer.

Drug delivery in the field of cancer has undergone a continuous revolution over the past few decades. Development of novel chemotherapeutic agents without the method of delivering them to the tumor site would find no practical application in uprooting the fatal disease of uncontrolled cell proliferation, cancer. This makes the development of drug carriers exceedingly essential for diagnostics and therapy alike. Nanotechnological science has gained impetus in the recent past and has found applications in a plethora of fields. It has managed to create an impact in the field of diagnostics, drug delivery and therapy, equally. Taxol®, a chemotherapeutic agent that was initially obtained from the bark of Taxus brevifolia, moved on to the semisynthetic approach for its synthesis to address the shortage of its natural source. This drug is partially soluble in water and its initial formulation with Cremophor EL manifested as anaphylactic reactions. To do away with these problems and others such as lower circulation time in blood and non-specificity, nanotechnology is now being looked at as a promising solution. Nanotechnological carriers aim at enhancing targetspecificity by functionalization, drug stabilization and preventing its degradation due to physiological conditions, pH, enzymes, etc., demonstrating an Enhanced Permeability and Retention (EPR) effect, prolonged blood circulation and thus better anti-tumor activity, while the side effects being almost negligible. The patents in this chapter aim to highlight how nanotechnology can find practical applications and how one or more than one drugs could be administered in vivo in a sustained fashion. The step-wise development in using this potent anticancer drug (Taxol) involved the use of human serum albumin associated compositions (Abraxane®), cremophor-free formulations (Capxol™, Genexol-PM™), numerous oil-in-water emulsions, liposomes and micelles, use of graphene quantum dots (GQDs) for bioimaging and drug delivery and the use of single-walled and multi-walled carbon nanotubes. It also allows the readers to explore nanodevices that can be turned on and off as and when the need be for localized drug delivery. Enabling the nanocarriers to modulate the pharmacokinetic and pharmacodynamic properties of the drug is another notable feature that some of these nanocarriers possess.

Cancer is one of the major causes of death worldwide. Most of the conventional anticancer chemotherapeutics have limited efficacy and toxic side effects. During the last decades, nanomedicine has sparked a rapidly growing interest in cancer therapy due to numerous advantages including efficient encapsulation of hydrophilic and hydrophobic drugs, enhanced cargo accumulation at the target site, reduced offtarget drug distribution, ease of administration, and minimized side effects. However, application of drug-loaded nanocarriers is restricted by slow and inefficient drug release at the pathological site. A promising approach to address this issue is the development of stimuli-responsive nanocarriers that can be triggered by exogenous physical or endogenous chemical or biochemical stimuli to release the anticancer drug. In this chapter, recent patents published on stimuli-sensitive nanocarriers which are responsive to either external stimuli (such as hyperthermia, magnetic field, light, and ultrasound) or internal stimuli (including acidic pH, certain enzymes, and redox condition) are discussed.

Autophagy (AP) is a cell recovery programme that plays a critical role by degrading dysfunctional organelles and misfolded proteins. Besides its position to maintain homeostasis, the contribution of AP to the development and progression of several pathological conditions, including cancer has been denoted. A significant number of findings indicate the involvement of AP-mediated cell survival in the progression of many tumors. However, the data in esophageal cancer (EC) appears to be less initiated. In this chapter, first definition, types and mechanisms of AP are described, and the following sections are focused on giving a clear view of the findings that communicate AP with oncogenesis and tumor progression in EC. Moreover, the use of several drugs, which are known to modulate AP (inhibitors [3-MA, Bafilomycin etc.] and inducers [Nimotuzumab etc.]) in the treatment of EC, is discussed.

Treatment of cancer using nanoparticle-based approaches being explored extensively to overcome the drawbacks associated with conventional treatment. Progress in nanotechnology for cancer therapy has led to the development of smart nanoformulations which improve the intracellular delivery of drugs due to their augmented multi-functionality and targeting potential. Smart nanoformulations are nano range particles which release the drug in accordance with the biological stimuli pre-existing at the disease site. This chapter summarizes most of the recent patents related to smart nanopreparations for cancer therapy. Such a smart system has shown to enhance the therapeutic effect of current standard treatment modalities such as chemotherapies and radiotherapies. Several polymeric nanoparticles were patented that destroy tumors by thermal energy deposition and thus enhanced tumor therapy. Patented thermoresponsive solid lipid nanoformulations which act as smart drug delivery systems showed temperature sensitivity (39°C-45°C) and release payload at target sites of cancerous cells. The pH-sensitive polymeric drug delivery system containing adornment acidic or basic groups to accept or donate protons in response to environmental pH showed accelerated drug release at the tumor site. A novel liposome linked thermosensitive peptide was invented which showed temperature dependent peptide shrinkage and drug release. Likewise, due to unique properties of metallic nanoparticles in imaging and diagnostic field, they are gaining interest widely as stimuli-sensitive drug delivery system. Gold nanoparticles can absorb light strongly and convert photon energy into heat quickly and efficiently escalating the temperature of a tumor cell (41°C-47°C) and thus destroying cancerous cells specifically. Coupling metallic nanoparticle properties with pH-sensitive targeting, resulted in an enhanced anti-tumor effect as observed in recently granted patents.

Cancer patients receiving chemotherapy treatment frequently experience adverse side effects, including the development of chemotherapy-induced peripheral neuropathy (CIPN) and muscle wasting. Investigation into the pathophysiological mechanisms responsible for these neuromuscular effects is crucial since associated symptoms including pain and muscle fatigue can lead to chemotherapy dose reduction or discontinuation, as well as long-term effects on patient mobility and quality of life. While patient symptoms may vary depending on the chemotherapy drug type and dosage regime, inflammation has been implicated as a common mediator responsible for the peripheral tissue effects associated with chemotherapy use. Although mitochondrial dysfunction has been recently investigated as a key underlying mechanism of CIPN and chemotherapy-induced muscle atrophy, there is a close association between mitochondrial dysfunction, oxidative stress and inflammation in biological systems. Host genetic factors have also been implicated in CIPN, and further genetic studies are therefore essential for identifying biomarkers of patient susceptibility, as well as assisting in the elucidation of candidate molecular pathways. Finally, another important consideration is the relationship between cancer-induced and chemotherapy-induced effects, given that chemotherapy can exacerbate cancer cachexia-related muscle wasting. Since cancer cachexia results from excessive systemic inflammation due to the host-tumour interaction, these findings suggest that inflammation-associated molecular alterations due to chemotherapy administration could contribute to muscle wasting in the treatment setting. Therefore, the purpose of this chapter is to provide evidence for a role of inflammation in chemotherapy-induced neuromuscular effects, and to summarise recent patented developments aimed at targeting these side effects.

Nutrition and dietary habits are investigated as environmental factors in cancer development and a strong relationship has been found between diet and cancer. Nutrients affect gene expression, gene regulation and eventually individuals’ genome. Genes related to carcinogen metabolism, steroid hormone metabolism and DNA repair are involved in cancer progress. Therefore, it is crucial to understand the factors affecting the change in cancer-related genes. Nutrigenomics is a new multidisciplinary field, investigating the effect of nutrients on genome and its expression through molecular techniques. Nutrigenomics enables to unveil how nutrients regulate cellular metabolism via gene and protein expressions and provide information on the functions of genome. The resulting differences or similarities in gene expressions as response to diets, will enable to understand diet-gene interactions at personalized levels that will implement the concept of personalized nutrition. The genetic variations among individuals will explain the health and disease status of human to be used to determine the cancer risk of individuals. In this chapter, it is aimed to review nutrient-cancer interaction, nutrigenomics approaches and patents related to the implications of nutrigenomics in cancer treatments.