Beyond DNA-targeting in Cancer Chemotherapy. Emerging Frontiers - A Review

Abstract

: Modern anticancer drugs target DNA specifically on rapid division of malignant cells. One downside of this approach is that they also target other rapidly dividing healthy cells such as those involved in hair growth leading to serious toxic side effects and hair loss. Therefore, it would be better to develop novel agents that address cellular signalling mechanisms unique to cancerous cells, and new research is now focussing on such approaches. Although the classical chemotherapy area involving DNA as the set target continues to produce important findings, nevertheless, a distinctly discernible emerging trend is the divergence from the cisplatin operation model that uses the metal as the primary active centre of the drug. Many successful anti-cancer drugs present are associated with elevated toxicity levels. Cancers also develop immunity against most therapies and the area of cancer research can therefore be seen as an area with a high unaddressed need. Hence, ongoing work into cancer pathogenesis is important to create accurate preclinical tests which can contribute to the development of innovative drugs to manage and treat cancer. Some of the emergent frontiers utilizing different approaches include nanoparticles delivery, use of quantum dots, metal complexes, tumour ablation, magnetic hypothermia and hyperthermia by use of Superparamagnetic Iron oxide Nanostructures, pathomics and radiomics, laser surgery and exosomes. This review summarizes these new approaches in good detail giving critical views with necessary comparisons. It also delves into what they carry for the future including their advantages and disadvantages.

The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization

“…Consequently, enormous efforts are being made to design more targeted therapies, including the synthesis of new drugs and the development of novel drug delivery approaches [17]. The research focused on innovative drugs that, unlike classical chemotherapeutics, do not include DNA targeting has recently gained momentum [18]. Furthermore, drug encapsulation has shown to be advantageous over direct administration of chemotherapeutic agents, providing enhanced drug pharmacokinetic and pharmacodynamic properties, targeted delivery, and reduced chemotoxicity [19].…”

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

“…DNA is a formidable molecular target for many drugs approved by the Food and Drug Administration (FDA), primarily for the treatment of cancer. − Despite the nonspecific cytotoxic character of traditional chemotherapeutics, modern drug discovery has promoted selective agents that target DNA and associated DNA processes. Alkylating agents nondiscriminately interact with DNA and often covalently in the form of cross-links.…”

Locoregional Thermal and Chemical Tumor Ablation: Review of Clinical Applications and Potential Opportunities for Use in Low- and Middle-Income Countries

“…RFA generates a high-frequency alternating current (200-1,200 kHz) through single (RFA) or multiple (stereotactic RFA) insulated needle electrodes inserted into tumors to induce ion oscillation in the extracellular fluid, producing local frictional heat from 50°C to 105°C. 16 - 18 Hyperthermic damage to cellular membranes and subcellular structures causes cell membrane dysfunction and protein denaturation, leading to cell death via acute coagulative necrosis. 19 , 20 Typically, 5-250 W of power is generated to obtain and maintain ablation temperatures for 10 seconds, up to 30 minutes, for a treatment section.…”

“… 35 MWA, however, achieves ablation temperatures and induces thermal coagulation faster than RFA due to deeper penetration of the microwave energy through various tissues and less susceptibility to the heat-sink effect. 16 , 18 The average ablation time of MWA procedures is less than RFA. 33 MWA is capable for ablation of larger tumors (up to approximately 6 cm) and can obtain similar therapeutic effects with fewer sessions.…”