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Interleukins in cancer: from biology to therapy.

Interleukins and associated cytokines serve as the means of communication for innate and adaptive immune cells as well as non-immune cells and tissues. Thus, interleukins have a critical role in cancer development, progression and control. Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects. This Review aims to unravel some of these complex interactio

The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptiv

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.

Glioblastoma multiforme (GBM) is the deadliest and the most heterogeneous brain cancer. The median survival time of GBM patients is approximately 8 to 15 months after initial diagnosis. GBM development is determined by numerous signaling pathways and is considered one of the most challenging and complicated-to-treat cancer types. Standard GBM therapy consist of surgery followed by radiotherapy or chemotherapy, and combined treatment. Current standard of care (SOC) does not offer a significant chance for GBM patients to combat cancer, and the selection of available drugs is limited. For almost

The Osteoclast in Bone Metastasis: Player and Target.

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenome

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in expe

Modulation of Lonp1 Activity by Small Compounds.

The Lon protease homolog 1 (LONP1) is an ATP-dependent mitochondrial protease essential for maintaining proteostasis, bioenergetics, and cellular homeostasis. LONP1 plays a pivotal role in protein quality control, mitochondrial DNA maintenance, and oxidative phosphorylation system (OXPHOS) regulation, particularly under stress conditions. Dysregulation of LONP1 has been implicated in various pathologies, including cancer, metabolic disorders, and reproductive diseases, positioning it as a promising pharmacological target. This review examines compounds that modulate LONP1 activity, categorizin

Nanoparticles Based Therapeutic Approaches in Oncogenic Viral Infections: A Review.

Nanotechnology has revolutionized biomedical research by providing novel strategies for the prevention, diagnosis, and treatment of oncogenic viral infections. Nanoparticles, possessing tunable physicochemical properties, enable targeted drug delivery, enhance vaccine efficacy, and facilitate advanced viral diagnostics, addressing key limitations of conventional therapies. Oncogenic viruses contribute substantially to the global burden of cancer through persistent infections and are influenced by environmental and lifestyle factors. The objective of this review is to synthesize and critically

Nanoparticles and bone microenvironment: a comprehensive review for malignant bone tumor diagnosis and treatment.

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applica

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… When donor DNA is provided as a homologous recombination template, the cell uses HDR to precisely insert, delete, or replace bases at specific locations. …

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and abs

Gene regulation by non-Coding RNAs in infertility: a mechanistic review.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remode

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta (γδ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendrit

Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomar

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… recombination repair genes; MCRPC, metastatic castrate resistant prostate cancer; MSM, myelodysplastic syndrome/myeloproliferative; pMMR, proficient mismatch repair; PP, primary peritoneal cancer; UC, urothelial cancer. … HRR Genes and PARP Inhibitors Researchers estimate that approximately 30–50% of ovarian cancers are associated with homologous recombination (HR) deficiency. …

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells

Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.

Glioblastoma (GB) is the most aggressive malignancy of the central nervous system. Despite two decades of intensive research since the establishment of the standard of care, emerging strategies have yet to produce consistent satisfactory outcomes. Because of its specific localisation and intricate characteristics, GB is a uniquely regulated solid tumour with a strong resistance to therapy. Advances in targeted radionuclide therapy (TRT), particularly with the introduction of a-emitting radionuclides, have unveiled potential avenues for the management of GB. Recent preclinical and clinical stud

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… PARPs are overexpressed in cancer, and tumours with defective homologous recombination may depend on PARP-mediated DNA repair, making them vulnerable to PARP inhibition 194 . PARP inhibitors (PARPi) have unveiled therapeutic potential in preclinical studies in GB mouse models 195 . … While SSBs are repaired through mechanisms such as base excision repair, nucleotide excision repair, and mismatch repair, DSBs are primarily repaired through homologous recombination and non-homologous end joining. …

Комплексный номер копий с высоким разрешением и гистомолекулярный анализ диффузной глиомы в масштабах полушария, H3 G34-mutant обнаруживает общие аномалии TP53.

Диффузная глиома в масштабах полушария, Н3 G34-mutant (В тыс.DHG-H3 G34 характеризуется главным образом молекулярным профилированием метилирования и исследованиями последовательности. Мы описываем комплексную гистомолекулярную оценку, включая профили копий с высоким разрешением серии 60 DHG-H3 G34 для дальнейшего понимания спектра генетических изменений, связанных с этим типом опухолей. Случаи были подвергнуты клиническому тестированию с использованием: 187-gene мутация и синтез были нацелены на нейроонтологию следующего поколения (n = 60) и онкосканского хромосомного микроаррара (n = 26) одно

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… Histone H3G34R mutation causes replication stress, homologous recombination defects and genomic instability in S. pombe . Elife. 2017;6:e27406. 30. Lowe BR, Yadav RK, Henry RA, Schreiner P, Matsuda A, Fernandez AG, et al. …