Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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Kawade et al.: Therapeutic potential of PI3K/Akt/mTOR signalling pathway Cell signalling mechanism plays a vital role in cell functioning. Imbalance and disregulation between these signals, such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signalling pathway may lead to uncontrolled cell proliferation. Generation of drug resistance is the hurdle in current cancer treatment. Designing an effective combination therapy for inhibition of two or more proteins of a given pathway might help to overcome the drug resistance and side effect related issues in cancer treatment. In this regard, application of computational tools firstly to predict newer combinations against phosphatidylinositol-3-kinase, protein kinase B and mammalian target of rapamycin involved in a single pathway have been proposed. The results obtained using the computational tools were shortlisted based on GlideScore and binding interactions of the drugs to the receptors of the pathway. One of the predicted combinations was further subjected to biological evaluation using the Western blot assay. The experimental results revealed synergistic effects that supported the predictions. The study also provided insights for the application and development of computational tools to predict newer combinations in a given network pharmacology.

Herbal toothpowders are available in market in a wide varieties, which consist of various ingredients. In rural areas of the developing countries, they are still used for cleansing teeth. Erythema multiforme (EM) is an acute mucocutaneous disorder that is believed to be a sequel of a cytotoxic immunologic attack on keratinocytes which express non-self-antigens. A 31-year-old male who used herbal toothpowder for oral-hygiene maintenance presented with ulcers in mouth, encrustation on lips and target lesions on both hands, suggesting Erythema multiforme. An oral biopsy confirmed the diagnosis. To the best of our knowledge, there is no report of an association of herbal extracts and EM in the English literature. With this report, we present a rare new triggering factor of Erythema mutiforme, thus adding it to the endless list of aetiologies.