Alternative approaches to target Cancer Modes of cell death and Endogenous H2S based drug release

Abstract

Cancer initiates when the somatic cells abandon their very innate collaborative nature and become selfish. Mutation, competition and natural selection are the characteristic behaviour of cancer where every individual prospers at the expense of their neighbour. This ultimately leads to the destruction of the whole organism. For over a century, researchers have focused on understanding the underlying mechanisms adapted by the cancer cells. The tumor cells need to constantly readapt to preserve their survival and growth in unfavorable conditions. This reflects multifactorial processes involving the induction of drug-detoxifying mechanism/overexpression of p-glycoproteins, cross-talks between different receptors in tumor microenvironment, dysregulation of cell cycle, apoptosis and DNA repair mechanisms, epigenetic modifications, the balance between increased protein synthesis and ER proteostasis, etc. Recent studies report that the signaling through gaseous transmitters (carbon monoxide, nitric oxide, and hydrogen sulfide) also plays a significant role in tumorigenesis. Several methods and approaches like surgery, chemotherapy, hormonal therapy, radiation therapy, immunotherapy, anti-angiogenic therapy, and nanotechnology-based therapies are currently practiced at a clinical level against cancer patients. Although these have proven useful in bringing effective treatment strategies against cancer to a greater extent, yet there are issues like drug-induced toxicity, delayed detection of cancer and resistance against chemotherapy. Therefore, we need to focus our research towards the development of newer approaches to target cancer. Paraptosis- an alternative cell death mechanism newlineAdvancement in cancer therapies demands a better understanding of the mechanism of cell death. Many chemotherapeutic agents and anti-tumor therapies are based on inducing apoptosis. Apoptosis is the stereotypical form of cell death that is dependent on caspase activation and involves nuclear condensation, DNA fragmentation, ..