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Chimeric antigen receptor T-cell therapy: challenges and opportunities in lung cancer.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the paradigm in hematological malignancies treatment, driving an ever-expanding number of basic research and clinical trials of genetically engineering T cells to treat solid tumors. CAR T-cell therapies based on the antibodies targeting Mesothelin, CEA, EGFR, EGFR, MUC1, DLL3, and emerging novel targets provide promising efficacy for lung cancer patients. However, clinical application of CAR T-cell therapy against lung cancer remains limited on account of physical and immune barriers, antigen escape and heterogeneity, on-target

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

Applications of Curcumin and Its Nanoforms in the Treatment of Cancer.

Due to the diverse medicinal and pharmacokinetic properties of turmeric, it is well-known in the therapeutic, pharmaceutic, nutraceutical, cosmetic, and dietary industries. It gained importance due to its multitude of properties, such as wound-healing, anti-inflammatory, anti-oxidant, anti-microbial, cytoprotective, anti-aging, anti-cancer, and immunomodulatory effects. Even though the natural healing effect of turmeric has been known to Indians as early as 2500 BCE, the global demand for turmeric has increased only recently. A major reason for the beneficiary activities of turmeric is the pre

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… Curcumin incorporated with metal oxide nanoparticles was assessed in A549 cells and was found to induce oxidation and ROS generation [ 87 ]. … The polymeric encapsulated form of curcumin induced anti-cancer activity in breast cancer (MDA-MB-231) and lung cancer (A549) cell lines by modulating the expression of hypoxia-inducing factors (HIF) and the p65 subunit (RelA) of the transcription factor, NF-κB. …

Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer.

Cancer constitutes a severe threat to human health and quality of life and is one of the most significant causes of morbidity and mortality worldwide. Natural dietary products have drawn substantial attention in cancer treatment and prevention due to their availability and absence of toxicity. Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors. This review summarizes recent publications on culture techniques, extraction processes, and anti-tumor applications of RA-enriched dietary supplements. We discuss techniqu

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… The RA-enriched fraction reduced reactive oxygen species (ROS) and inhibited invasion through the NF-κB pathway in A549 cells [ 21 , 22 ]. Melissa officinalis L. is a traditional herbal tea from the Mediterranean. Studies found that M. officinalis L. with ethanol extraction enriched RA [ 8 , 23 ]. … Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways Biomolecules 2021 11 1090 10.3390/biom11081090 34439757 PMC8392772 23. Encalada M.A. Hoyos K.M. …

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin-proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article "PROTACs:

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… cells, which led to the selective growth inhibition of EGFR mutant lung cancer cells instead of normal cells or A549 cells. … In MCF-7 and A549 cells, the obvious degradation of IGF-1R and Src could be observed at the concentration of 5 µM. Although the degradation effect was poor, it showed obvious antiproliferative activity on MCF-7 and A549 cells, and the IC 50 were 3.3 µM, 2.7 µM and 4.2 µM, 7.6 µM, respectively. …

Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.

Edible salty-flavored Chinese materia medica (ESCM) refers to a category of traditional Chinese medicine (TCM) that also serve as food, characterized by their salty flavor. According to the TCM theory, ESCM can soften and disperse knots, thus potentially offering benefits for cancer prevention and treatment. With cancer remaining a major global health challenge, its primary prevention strategies, especially through dietary modification, are crucial. ESCM have recently garnered substantial attention, due to their remarkable clinical efficacy and low side-effect profile. Researches on ESCM demon

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… Guo et al. reported that quercetin elevates the SIRT1 expression level and the AMPK phosphorylation level in a dose-dependent manner, thereby activating the SIRT1/AMPK axis to trigger mitochondria-dependent apoptotic pathway in human A549 cells and H1299 cells, to treat the non-small cell lung cancer … In NSCLC A549 cells, kaempferol effectively blocks TGF-β1-induced EMT and cell metastasis by reestablishing E-cadherin expression and inhibiting MMP-2 and TGF-β1 upregulation ( Zhu et al., 2021 ). …

Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.

The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, d

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… The tumor suppressor candidate 3 (TUSC3) inhibited cell growth and induced apoptosis in A549 cells. … The loss of TUSC3 in A549 cells inhibits autophagy by increasing the SQSTM1/p62 expression [ 262 ]. Other studies have described a nuclear induction of β-catenin in human pancreatic cancer cells by SAHA, which resulted in an inhibition of cell proliferation and in apoptosis induction [ 263 ]. …

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

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… Emodin treatment in A549 cells resulted in the inactivation of AKT and ERK and formation of ROS, Further, it disrupted the mitochondrial membrane potential and reduced the levels of mitochondrial Bcl-2 and increased the mitochondrial Bax levels ( Akkol et al., 2021 ). … Inhibition of TNF-α-Induced NF-κ B Activation and IL-8 Release in A549 Cells with the Proteasome Inhibitor MG-132. Am. J. Respir. Cel Mol. Biol. 19 (2), 259–268. 10.1165/ajrcmb.19.2.3149 Fischer S. M., Lo H. H., Gordon G. B., Seibert K., Kelloff G., Lubet R. A., et al. (1999). …

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

Upcoming Revolutionary Paths in Preclinical Modeling of Pancreatic Adenocarcinoma.

To date, PDAC remains the cancer having the worst prognosis with mortality rates constantly on the rise. Efficient cures are still absent, despite all attempts to understand the aggressive physiopathology underlying this disease. A major stumbling block is the outdated preclinical modeling strategies applied in assessing effectiveness of novel anticancer therapeutics. Current in vitro preclinical models have a low fidelity to mimic the exact architectural and functional complexity of PDAC tumor found in human set, due to the lack of major components such as immune system and tumor microenviron

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… Cancer associated fibroblast-derived hepatocyte growth factor inhibits the paclitaxel-induced apoptosis of lung cancer A549 cells by up-regulating the PI3K/Akt and GRP78 signaling on a microfluidic platform. PLoS ONE. (2015) 10:e0129593. 10.1371/journal.pone.0129593 93. …

Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer.

AimSSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted.ResultsHigh levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed.ConclusionIncreases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmati

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resi

Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.

Recent studies highlight the multifaceted roles of neurotransmitters in tumor immunomodulation, offering novel avenues for increasing therapeutic efficacy. These signaling molecules are classified into cholinergic agents, monoamines, amino acids, and peptides and regulate tumorigenesis, metastasis, and immune evasion via autocrine/paracrine pathways and receptor-mediated interactions. Notably, neurotransmitters influence tumor cell proliferation, apoptosis, and immune cell activity by modulating intracellular signaling cascades through posttranslational modifications (serotonylation and dopami

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

The role of interleukin-17 in inflammation-related cancers.

Emerging evidence indicates a correlation between inflammation and the development and progression of cancer. Among the various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as a critical link between inflammation and cancer. IL-17 is a highly versatile pro-inflammatory cytokine that plays a pivotal role in host defense, tissue repair, the pathogenesis of inflammatory diseases, and cancer progression. During the early stages of tumorigenesis, IL-17 signaling directly promotes the proliferation of tumor cells. Conversely, IL-17 has been shown to exhibit antitumor immunity

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances p

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases.

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae a

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

"Smart" drug delivery: A window to future of translational medicine.

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and e

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… cell lines | **** | Purushothaman et al. (2021) DGNP Loaded and Folate | Folic acid | Folate receptor | Doxorubicin | ovarian | A2780, OVCAR3 and SKOV3 cell lines | CD-1 female nude mice | Ak et al. (2018) Attached Erythrocyte Vesicles (FVzDGNP) PFH/DOX@PLGA/Fe3O4-FA | Folic acid | Folate receptor | … With high drug loading, a longer half-life in the circulation, lower toxicity, and an antiproliferative effect of PTX on A549 cells, this co-delivery system is a promising SDDS ( Jin et al., 2018 ). 5.2 Inorganic based SDDSs 5.2.1 Carbon nanotubes (CNTs) CNTs have attracted incredible interest in …

CXCR4: A Promising Novel Strategy for Lung Cancer Treatment.

Lung cancer remains a major public health challenge due to high incidence and mortality. The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) constitute a critical axis in tumor biology, influencing tumor cell proliferation, invasion, angiogenesis, and immune evasion. Aberrant CXCR4 expression is frequently observed in lung cancer and is closely associated with adverse prognosis, enhanced metastatic potential, and therapeutic resistance. Mechanistically, CXCR4 activates signaling pathways including PI3K/AKT, MAPK/ERK, JAK/STAT, and FAK/Src, promoting epithelial-mesenchymal transition, st

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… In the NSCLC cell line A549 cells, lncRNA NORAD can downregulate CXCR4 levels, significantly inhibiting cell proliferation, migration, and invasion [ 67 ]. … In addition to these pathways, a novel autocrine signaling loop has been identified in CXCR4 -overexpressing lung cancer A549 cells. …