Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

Role of calcium ion (Ca²⁺) in the functioning of neurons from their naïve state to mature state is of vital importance. It controls functions such as neuronal functioning, neuronal ATP production, central nervous system migration and many others. Failure in Ca²⁺ homeostasis mechanisms and the resulting cellular Ca²⁺ ion load initiates a cascade of reactions involving various cytosolic enzymes and proteins. This total mechanism leads to the neuronal death. The ability of neurons to resist such death mechanisms fails as a result of extensive cell death signaling cascade reactions and later brings brain damage. The role of neuronal endoplasmic reticulum and protein channels like CaVs, TRP channels, and NMDAR as the mediators of cell damage and death has been evaluated in the studies related to cerebral ischemia. Here, we portray Ca²⁺ ion as one of the role players in neuronal death and cerebral damage following ischemia. The role of Ca²⁺ in neuronal functioning, its regulatory mechanisms and the failure of homeostatic mechanisms are discussed in detail.

Every year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far. Hypoxia-inducible factor-1 (HIF-1) plays a crucial role in the transcriptional adaptation of cells to hypoxia. Small molecule-based hypoxia-mimetic agents either stabilize HIF-1α via HIF-prolyl hydroxylases (PHDs) inhibition or through other mechanisms. In both the cases, these agents have been shown to confer ischemic neuroprotection in vitro and in vivo. The agents which act via PHD inhibition are mainly classified into iron chelators, iron competitors, and 2 oxoglutarate (2OG) analogs. This review discusses HIF structure and key players in the HIF-1 degradation pathway as well as the genes, proteins and chemical molecules that are connected to HIF-1 and how they affect cell survival following ischemic injury. Furthermore, this review gives a summary of studies that used PHD inhibitors and other HIF-1α stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury.

Conventional knowledge considered apoptosis as the sole form of programmed cell death during development, homeostasis and diseases, whereas necrosis was regarded as an unregulated and uncontrollable process. Recent revelations suggest that necrosis can also occur in a regulated, caspase-independent manner and shares characteristics with both necrosis and apoptosis. The major cell death processes namely apoptosis, autophagy and necrosis are interlinked and contain many common regulatory mechanisms. Mounting evidence indicates that necroptosis contributes to the pathogenesis of various diseases, including ischemic stroke, traumatic brain injury, neurodegenerative disorders and brain tumor. We present here an overview of the molecular mechanisms governing necroptosis and its connection with apoptosis and autophagy processes. Further, the necroptosis mechanisms underlying the neurodegeneration during ischemia reperfusion (I/R) injury are described, with an emphasis on the key proteins involved in this type of cell death. Knowledge regarding programmed cell death (PCD) with relevance to necroptosis may play a significant role in debilitating brain disorders.