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Topic Review
Drug Delivery Systems Polymeric Nanocarriers in Cancer Therapy
Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules that interact with DNA and cause cell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, and they can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specifically target cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs).
  • 2.4K
  • 25 Mar 2022
Topic Review
DUX4-rearranged leukaemia
DUX4-rearrangement (DUX4r) is a recently discovered recurrent genomic lesion reported in 4-7% of B cell acute lymphoblastic leukaemia (B-ALL). The gene fusion most commonly links the hypervariable IGH gene to DUX4 a gene located within the D4Z4 macrosatellite repeat on chromosome 4. DUX4r is cryptic to most standard diagnostic techniques and difficult to identify even with next-generation sequencing assays.
  • 2.4K
  • 15 Oct 2020
Topic Review
Stimuli-Responsive Drug Delivery Systems
Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis.
  • 2.4K
  • 10 Mar 2021
Topic Review
Targeting hypoxia-driven metabolic reprogramming
Hypoxia-driven metabolic adaptation of cancer cells revolutionizes the current understanding of hypoxia-associated tumor development and progression. Several hypoxia-responsive molecular determinants, such as hypoxia-inducible factors, guide the cellular adaptation to hypoxia by gene activation, which is critical for promoting malignant progression in the hostile tumor microenvironment. This article fully recaps the major research progress in this topic in order to assess its potential as a targetable pathway to better combat cancer and overcome treatment resistance. Knowledge from this article facilitates cancer researchers to sharpen their focus on gaining mechanistic insights into metabolic transformation in hypoxic cancers and developing novel strategies to target tumor metabolic rewiring driven by hypoxia, which would open avenues to improve the management of tumor hypoxia.
  • 2.4K
  • 11 Aug 2020
Topic Review
CBL Mutations
CBL mutations are progressively being described as involved in different clinical manifestations. Somatic CBL mutations can be found in different type of cancer. The clinical spectrum of germline mutations configures the so-called CBL syndrome, a cancer-predisposing condition that includes multisystemic involvement characterized by variable phenotypic expression and expressivity.
  • 2.4K
  • 24 Feb 2022
Topic Review
P-Glycoprotein
P-glycoprotein (P-gp) is a crucial membrane transporter situated on the cell’s apical surface, being responsible for eliminating xenobiotics and endobiotics. P-gp modulators are compounds that can directly or indirectly affect this protein, leading to changes in its expression and function. These modulators can act as inhibitors, inducers, or activators, potentially causing drug–drug interactions (DDIs). 
  • 2.4K
  • 15 Nov 2023
Topic Review
Chemoresistance in Breast Cancers
Despite the leaps and bounds in achieving success in the management and treatment of breast cancers through surgery, chemotherapy, and radiotherapy, breast cancer remains the most frequently occurring cancer in women and the most common cause of cancer-related deaths among women. Systemic therapeutic approaches, such as chemotherapy, although beneficial in treating and curing breast cancer subjects with localized breast tumors, tend to fail in metastatic cases of the disease due to (a) an acquired resistance to the chemotherapeutic drug and (b) the development of intrinsic resistance to therapy. The existence of cancer stem cells (CSCs) plays a crucial role in both acquired and intrinsic chemoresistance. CSCs are less abundant than terminally differentiated cancer cells and confer chemoresistance through a unique altered metabolism and capability to evade the immune response system. Furthermore, CSCs possess active DNA repair systems, transporters that support multidrug resistance (MDR), advanced detoxification processes, and the ability to self-renew and differentiate into tumor progenitor cells, thereby supporting cancer invasion, metastasis, and recurrence/relapse. Hence, current research is focusing on targeting CSCs to overcome resistance and improve the efficacy of the treatment and management of breast cancer. Studies revealed that metformin (1, 1-dimethylbiguanide), a widely used anti-hyperglycemic agent, sensitizes tumor response to various chemotherapeutic drugs. Metformin selectively targets CSCs and improves the hypoxic microenvironment, suppresses the tumor metastasis and inflammation, as well as regulates the metabolic programming, induces apoptosis, and reverses epithelial–mesenchymal transition and MDR. Here, we discuss cancer (breast cancer) and chemoresistance, the molecular mechanisms of chemoresistance in breast cancers, and metformin as a chemo-sensitizing/re-sensitizing agent, with a particular focus on breast CSCs as a critical contributing factor to acquired and intrinsic chemoresistance. The review outlines the prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer/chemo-sensitizing drug in the treatment of breast cancer. It intends to provide a rationale for the use of metformin as a combinatory therapy in a clinical setting.
  • 2.3K
  • 15 Sep 2020
Topic Review
Targeting NF-κB Signaling for MM
Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease.
  • 2.3K
  • 27 Oct 2020
Topic Review
CXCL13 in Cancer and Other Diseases
C-X-C chemokine ligand 13 (CXCL13) and its receptor, CXCR5, make crucial contributions to this process by triggering intracellular signaling cascades in malignant cells and modulating the sophisticated TME in an autocrine or paracrine fashion. The CXCL13/CXCR5 axis has a dominant role in B cell recruitment and tertiary lymphoid structure formation, which activate immune responses against some tumors. In most cancer types, the CXCL13/CXCR5 axis mediates pro-neoplastic immune reactions by recruiting suppressive immune cells into tumor tissues. Tobacco smoke and haze (smohaze) and the carcinogen benzo(a)pyrene induce the secretion of CXCL13 by lung epithelial cells, which contributes to environmental lung carcinogenesis. 
  • 2.3K
  • 09 Dec 2021
Topic Review
ALBI Grades
Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Selection of therapeutic modalities and the prognosis of affected patients are well known to be dependent not only on tumor burden, but also hepatic reserve function. Anti-viral treatments for chronic hepatitis related to a viral infection and an increase in cases of non-viral HCC associated with the aging of society have resulted in dramatic changes regarding the characteristics of HCC patients. With recent developments in therapeutic modalities for HCC, more detailed assessment of hepatic function has become an important need. Studies in which the relationship of albumin-bilirubin (ALBI) with prognosis of HCC patients was investigated were reviewed in order to evaluate the usefulness of newly developed ALBI and modified ALBI (mALBI) grades for HCC treatment, as those scoring methods are considered helpful for predicting prognosis and selecting therapeutic modalities based on expected prognosis.
  • 2.3K
  • 27 Oct 2020
Topic Review
(Endo)Cannabinoids and Gynaecological Cancers
Gynaecological cancers can be primary neoplasms, originating either from the reproductive tract or the products of conception, or secondary neoplasms, representative of metastatic disease. For some of these cancers, the exact causes are unknown; however, it is recognised that the precise aetiopathogeneses for most are multifactorial and include exogenous (such as diet) and endogenous factors (such as genetic predisposition), which mutually interact in a complex manner. One factor that has been recognised to be involved in the pathogenesis and progression of gynaecological cancers is the endocannabinoid system (ECS). The ECS consists of endocannabinoids (bioactive lipids), their receptors, and metabolic enzymes responsible for their synthesis and degradation.
  • 2.3K
  • 31 Aug 2021
Topic Review
Protein Subcellular Localization
Proteins are localized into different cellular compartments and sub-compartments inside the cell. Each subcellular compartment has a distinct well-defined function in the cell and has a characteristic physicochemical environment, which drives proper functioning of the proteins. Each subcellular compartment has a distinct, well defined function in the cell and is considered to have evolved from the prokaryotic cell. Typical eukaryotic cells have two types of DNAs (i) chromosomal nuclear DNA and (ii) organelle DNA, which is present in mitochondria and chloroplast while prokaryotic cells have only single type of DNA called nucleoid.
  • 2.3K
  • 18 Feb 2021
Topic Review
Luteolin
Luteolin (3′,4′,5,7-tetrahydroxyflavone), a member of the flavonoid family derived from plants and fruits, shows a wide range of biomedical applications. In fact, due to its anti-inflammatory, antioxidant and immunomodulatory activities, Asian medicine has been using luteolin for centuries to treat several human diseases, including arthritis, rheumatism, hypertension, neurodegenerative disorders and various infections. Of note, luteolin displays many anti-cancer/anti-metastatic properties.
  • 2.3K
  • 01 Jun 2023
Topic Review
Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment
Cancer is characterized by persistent cell proliferation driven by aberrant cell cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing and potential approach for the development of antitumor medicines is the suppression of CDKs that lead to induction of apoptosis and cell cycle arrest. The shift of the cell cycle from the G0/G1 phase to the S phase, which is characterized by active transcription and synthesis, depends on the development of the cyclin D-CDK4/6 complex. A precise balance between anticancer activity and general toxicity is demonstrated by CDK inhibitors, which can specifically block CDK4/6 and control the cell cycle by reducing the G1 to S phase transition. 
  • 2.3K
  • 08 Feb 2023
Topic Review
Role of Lactobacillus in the Female Reproductive Tract
The eubiotic vaginal microbiota of reproductive-aged women is composed mostly of various Lactobacillus species (spp.), which exert protective effects via the production of lactic acid, bacteriocins, polysaccharides, peptidoglycans, and hydrogen peroxide (H2O2), lowering pH, raising the viscosity of cervicovaginal mucus, and hampering both the adhesion of cells to epithelial tissue and the entry of HPV. The depletion of beneficial microorganisms could increase the risk of sexually transmitted infections. Emerging therapies involve mucosal, intranasal vaccines, which trigger systemic and mucosal immune responses, thus protecting against HPV-induced tumours.
  • 2.3K
  • 18 Oct 2022
Topic Review
Transforming Growth Factor-β
Transforming growth factor-β (TGF-β) was originally identified as an anti-tumour cytokine. However, there is increasing evidence that it has important roles in the tumour microenvironment (TME) in facilitating cancer progression. TGF-β actively shapes the TME via modulating the host immunity. These actions are highly cell-type specific and complicated, involving both canonical and non-canonical pathways. In this review, we systemically update how TGF-β signalling acts as a checkpoint regulator for cancer immunomodulation. A better appreciation of the underlying pathogenic mechanisms at the molecular level can lead to the discovery of novel and more effective therapeutic strategies for cancer.
  • 2.3K
  • 16 Nov 2020
Topic Review
Nonsense-Mediated mRNA Decay
Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a surveillance pathway used by cells to control the quality mRNAs and to fine-tune transcript abundance. NMD plays an important role in cell cycle regulation, cell viability, DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism caused by genetic mutations or dys-regulation of the NMD pathway can lead to pathologies, including neurological disorders, immune diseases and cancers. The role of NMD in cancer development is complex, acting as both a promoter and a barrier to tumour progression. Cancer cells can exploit NMD for the downregulation of key tumour suppressor genes, or tumours adjust NMD activity to adapt to an aggressive immune microenvironment.
  • 2.3K
  • 22 Sep 2021
Topic Review
Targeting p53-MDM2 Interaction for Cancer Drug Discovery
Named as the guardian of the genome, p53 is a tumor suppressor that regulates cell function, often through many different mechanisms such as DNA repair, apoptosis, cell cycle arrest, senescence, metabolism, and autophagy. One of the genes that p53 activates is MDM2, which forms a negative feedback loop since MDM2 induces the degradation of p53. When p53 activity is inhibited, damaged cells do not undergo cell cycle arrest or apoptosis. As 50% of human cancers inactivate p53 by mutation, current research focuses on reactivating p53 by developing drugs that target the p53-MDM2 interaction, which includes the binding of MDM2 and phosphorylation of p53.
  • 2.3K
  • 22 Jul 2022
Topic Review
Microneedles for Cancer Treatment
Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small and large molecules to the subjects in need thereof. There exist several strategies for drug delivery using MNs, wherein each strategy has its pros and cons. Research in this domain lead to product development and commercialization for clinical use. Additionally, several MN-based products are undergoing clinical trials to evaluate its safety, efficacy, and tolerability. 
  • 2.3K
  • 10 Jan 2021
Topic Review
Melatonin and Liver Cancer
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with beneficial effects in a broad number of tumors, including the primary liver cancers hepatocarcinoma (HCC) and cholangiocarcinoma (CCA). Among them, melatonin has shown to modulate different cancer-associated processes and enhance drug efficacy against HCC and CCA. Therefore, melatonin has a potential role in improving the current therapeutic landscape in these liver tumors.
  • 2.2K
  • 12 Oct 2021
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