Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis

Tamoxifen is commonly prescribed for preventing recurrence in patients with breast cancer. However, the responses of the patients on tamoxifen treatment are variable. Cytochrome P450 genetic variants have been reported to have a significant impact on the clinical outcomes of tamoxifen treatment but no tangible conclusion can be made up till now. The present review attempts to provide a comprehensive review on the associative relationship between genetic polymorphisms in cytochrome P450 enzymes and survival in breast cancer patients on adjuvant tamoxifen therapy. The literature search was conducted using five databases, resulting in the inclusion of 58 studies in the review. An appraisal of the reporting quality of the included studies was conducted using the assessment tool from the Effective Public Health Practice Project (EPHPP). Meta-analyses were performed on CYP2D6 studies using Review Manager 5.3 software. For other studies, descriptive analyses were performed. The results of meta-analyses demonstrated that shorter overall survival, disease-free survival and relapse-free survival were found in the patients with decreased metabolisers when compared to normal metabolisers. The findings also showed that varying and conflicting results were reported by the included studies. The possible explanations for the variable results are discussed in this review.

GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy

Pyroptosis is a recently identified mechanism of programmed cell death related to Caspase-1 that triggers a series of inflammatory reactions by releasing several proinflammatory factors such as IL-1β and IL-18. The process is characterised by the rupture of cell membranes and the release of cell contents through the mediation of gasdermin (GSDM) proteins. GSDMD is an important member of the GSDM family and plays a critical role in the two pathways of pyroptosis. Diabetic nephropathy (DN) is a microvascular complication of diabetes and a major cause of end-stage renal disease. Recently, it was revealed that GSDMD-mediated pyroptosis plays an important role in the occurrence and development of DN. In this review, we focus on two types of kidney cells, tubular epithelial cells and renal podocytes, to illustrate the mechanism of pyroptosis in DN and provide new ideas for the prevention, early diagnosis and molecular therapy of DN.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers

Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.

Alveolar macrophages: novel therapeutic targets for respiratory diseases

Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

Targeting unfolded protein response: a new horizon for disease control

Unfolded protein response (UPR) is an evolutionarily conserved pathway triggered during perturbation of endoplasmic reticulum (ER) homeostasis in response to the accumulation of unfolded/misfolded proteins under various stress conditions like viral infection, diseased states etc. It is an adaptive signalling cascade with the main purpose of relieving the stress from the ER, which may otherwise lead to the initiation of cell death via apoptosis. ER stress if prolonged, contribute to the aetiology of various diseases like cancer, type II diabetes, neurodegenerative diseases, viral infections etc. Understanding the role of UPR in disease progression will help design pharmacological drugs targeting the sensors of signalling cascade acting as potential therapeutic agents against various diseases. The current review aims at highlighting the relevance of different pathways of UPR in disease progression and control, including the available pharmaceutical interventions responsible for ameliorating diseased state via modulating UPR pathways.

Biological bases of cancer immunotherapy

Immunotherapy has changed the landscape of cancer treatment and has significantly improved the outcome of several cancer types including breast, lung, colorectal and prostate. Neoantigen recognition and immune checkpoint inhibitors are nowadays the milestones of different immunotherapeutic regimes; however, high cost, primary and acquired resistance and the high variability of responses make their extensive use difficult. The development of better predictive biomarkers that represent tumour diversity shows promise because there is a significant body of clinical data showing a spectrum of immunotherapeutic responses that might be related back to their specific characteristics. This article makes a conceptual and historical review to summarise the main advances in our understanding of the role of the immune system in cancer, while describing the methodological details that have been successfully implemented on cancer treatments and that may hold the key to improved therapeutic approaches.