The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.

Translation into Russian:  Tomasetti, C. , Li, L. , & Vogelstein, B.  (2017).  Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention . Science ,  355 (6331), 1330-1334. DOI:  10.1126/science.aaf9011

Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

https://www.hal.inserm.fr/inserm-01947474/document

Dormant, quiescent, tolerant and persister cells: Four synonyms for the same target in cancer.

Crosstalk between Raf-MEK-ERK and PI3K-Akt-GSK3β signaling networks promotes chemoresistance, invasion/migration and stemness via expression of CD44 variants (v4 and v6) in oral cancer

Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver. In addition to conversion of the acetaldehyde molecule, ALDH is also involved in other cellular functions. Recently, many studies have investigated the involvement of ALDH expression in viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. Notably, ALDH2 expression has been linked with liver cancer risk, as well as pathogenesis and prognosis, and has emerged as a promising therapeutic target. Of note, approximately 8% of the world's population, and approximately 30-40% of the population in East Asia carry an inactive ALDH2 gene. This review summarizes new progress in understanding tissue-specific acetaldehyde metabolism by ALDH2 as well as the association of ALDH2 gene polymorphisms with liver disease and cancer. New research directions emerging in the field are also briefly discussed.

/pdf/aldehyde-dehydrogenase-liver-disease-and-cancer-5f5w8cpzkb.pdf

Aldehyde Dehydrogenase, Liver Disease and Cancer.

Terpenes, also known as terpenoids are the largest and most diverse group of naturally occurring compounds. Based on the number of isoprene units they have, they are classified as mono, di, tri, tetra, and sesquiterpenes. They are mostly found in plants and form the major constituent of essential oils from plants. Among the natural products that provide medical benefits for an organism, terpenes play a major and variety of roles. The common plant sources of terpenes are tea, thyme, cannabis, Spanish sage, and citrus fruits (e.g., lemon, orange, mandarin). Terpenes have a wide range of medicinal uses among which antiplasmodial activity is notable as its mechanism of action is similar to the popular antimalarial drug in use—chloroquine. Monoterpenes specifically are widely studied for their antiviral property. With growing incidents of cancer and diabetes in modern world, terpenes also have the potential to serve as anticancer and antidiabetic reagents. Along with these properties, terpenes also allow for flexibility in route of administration and suppression of side effects. Certain terpenes were widely used in natural folk medicine. One such terpene is curcumin which holds anti-inflammatory, antioxidant, anticancer, antiseptic, antiplasmodial, astringent, digestive, diuretic, and many other properties. Curcumin has also become a recent trend in healthy foods and open doors for several medical researches. This chapter summarizes the various terpenes, their sources, medicinal properties, mechanism of action, and the recent studies that are underway for designing terpenes as a lead molecule in the modern medicine.

/pdf/therapeutic-and-medicinal-uses-of-terpenes-3g8jy41rw2.pdf

Therapeutic and Medicinal Uses of Terpenes

Cancer stem cells (CSCs) have gained an increasing attention recently in cancer research. CSCs have ability to generate new tumor through their stem cell properties, essentially self-renewal potential and differentiation into multiple cell lineages. Extensive evidences report that CSCs are resistant to many conventional therapies and mediate tumor recurrence. CSCs of lung cancer are well recognized by their specific markers such as CD133, CD44, ABCG2 and ALDH1A1 together with the CSC characteristics including spheroid and colony formation. Targeting these surface proteins with blocking antibodies and inhibition of ABC transporters and aldehyde dehydrogenase (ALDH) enzymes with small molecules may prove useful in inhibiting tumor progression. The Hh, Notch and Wnt pathways are key signaling cascades that govern cell fate during development and have been shown to be involved in CSCs in various solid tumors. Therapeutic approaches also target these signaling pathways in repressing the tumor progression. This review will focus on stem cell origins, role of signaling pathways, stem cell markers and therapeutic approaches specific to lung cancer.

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Lung cancer stem cells—origin, characteristics and therapy

Small cell lung cancer, a subtype of lung cancer is an extremely malignant disease due to its metastases and recurrence. Patients with SCLC develop resistance to chemotherapy and the disease relapses. This relapse and resistance are attributed to the heterogeneity of SCLC. Various factors such as recurrent mutations in key regulatory genes such as TP53, RB1, and myc, epigenetic changes, and cancer stem cells contribute to the observed heterogeneity. Cancer stem cell models predict neuroendocrine origin of SCLC. Though an unambiguous established CSC marker has not been assigned, markers CD133, CD44 have been found associated with SCLC. Genetically engineered mouse models (GEMMs) allow the validation of driver mutations and are necessary for design of targeted therapy. This chapter outlines the factors contributing to SCLC heterogeneity, detection methods, and the current therapy trials.

Heterogeneity of Small Cell Lung Cancer Stem Cells.

Microstructural, mechanical and corrosion behaviour of B_4C/BN-reinforced Al7075 matrix hybrid composites

Functional characterization of 1-aminocyclopropane-1-carboxylic acid oxidase gene in Arabidopsis thaliana and its potential in providing flood tolerance.

Niveditha Ramadoss

Papers

Therapeutic and Medicinal Uses of Terpenes

Lung cancer stem cells—origin, characteristics and therapy

Heterogeneity of Small Cell Lung Cancer Stem Cells.

Microstructural, mechanical and corrosion behaviour of B_4C/BN-reinforced Al7075 matrix hybrid composites

Functional characterization of 1-aminocyclopropane-1-carboxylic acid oxidase gene in Arabidopsis thaliana and its potential in providing flood tolerance.