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Topic Review
Cisplatin
Cisplatin, also referred to as cis-diamminedichloroplatinum (II) (CDDP), is a widely used, Pt-based anti-cancer chemotherapeutic agent. This transition metal coordination complex has a square planar molecular geometry and presents as a solid, yellow powder at room temperature. CDDP is fairly insoluble in most substances; however, it can be dissolved in dimethylformamide, and is somewhat soluble in water, but most preferable in saline sodium. In solid form, CDDP is stable for about two years if stored at room temperature in dry conditions and light protected; however, it is known to convert slowly to its trans-form. The stability of CDDP in sodium chloride solution is dependent on the chloride ion concentration; it is more stable when suspended in normal saline (0.9% sodium chloride). Saline also provides a reno-protective function, increasing hydration and aiding in excretion of CDDP from the kidneys.
  • 1.7K
  • 14 Dec 2022
Topic Review
Natural Blockers of PD-1/PD-L1 Interaction
The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. 
  • 1.7K
  • 11 Jan 2023
Topic Review
Glioblastoma Pathogenesis
Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma.
  • 1.7K
  • 28 Dec 2020
Topic Review
Cisplatin-Induced Ototoxicity
Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma.
  • 1.7K
  • 30 Nov 2023
Topic Review
Electroporation based treatments in Urology
The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides the possibility of transmission of genes across the cell membrane. As the protocols of gene electrotransfer (GET) over the last few years have improved, EP has become a well-known technique for non-viral cell transfection. GET involves DNA transfection directly to the cancer or the host skin and muscle tissue. Among urological cancers, the GET of several plasmids encoding prostate cancer antigens has been investigated in clinical trials.
  • 1.7K
  • 25 Aug 2020
Topic Review
Structure and Function of Sorting Nexin 27
SNX27 belongs to the sorting nexin (SNX) family of proteins that play a critical role in protein sorting and trafficking in the endocytosis pathway. This protein family is characterized by the presence of a Phox (PX) domain; however, SNX27 is unique in containing an additional PDZ (post-synaptic density 95/discs large/zonula occludens-1) domain.
  • 1.7K
  • 29 Jan 2023
Topic Review
DNA Polymerases
Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. 
  • 1.7K
  • 14 Dec 2020
Topic Review
ZEB Family
Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of EMT mechanism, therefore reducing metastasis. Also, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.
  • 1.7K
  • 19 Jul 2020
Topic Review
Immunogenic Cell Death in Cancer
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD).
  • 1.7K
  • 25 Dec 2020
Topic Review
Fundamental Principles in Electromotive Enhanced Drug Administration
Local-regional administration of cytotoxic drugs is an important adjunct to systemic chemotherapy amongst cancer patients. It allows for targeted delivery of agents at high concentration to target sites while minimizing systemic side effects. Despite the pharmacokinetic advantages of the local–regional approach, drug transport into tumor nodules remains limited due to the biophysical properties of these tissues. Electromotive enhanced drug administration (EMDA) represents a potential solution to overcome challenges in local drug transport by applying electric currents. Through electrokinetic phenomena of electromigration, electroosmosis and electroporation, electric currents have been shown to improve drug penetration and distribution in a wide variety of clinical applications.
  • 1.7K
  • 26 Oct 2022
Topic Review
Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. PDAC remains a devastating disease, despite extensive research efforts focused on the discovery of early diagnostic biomarkers and efficient therapeutic approaches, showing a high resistance to treatment that significantly contributes to poor survival. The success of epi-drugs in hematological malignancies and the robust body of evidence supporting the hypothesis about their ability to synergize with other anti-cancer drugs, sensitizing resistant tumor cells in preclinical models, have encouraged the search for these agents suitable for the future clinical management of PDAC.
  • 1.7K
  • 27 Oct 2020
Topic Review
T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles
Extracellular vesicles (EV) are a very diverse group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular exchange, both nearby and systemically, since they induce signals and transmit their cargo (proteins, lipids, miRNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. However, cell surface receptor-induced EV release is limited to cells from the immune system, including T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptors for antigen and several bioactive molecules, including proapoptotic proteins. These EV are specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy.
  • 1.7K
  • 29 Mar 2022
Topic Review
Targeting Tumor-Associated Macrophages
Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. 
  • 1.7K
  • 06 May 2021
Topic Review
Aurora Kinases in Lung Cancer
Lung cancer has remained one of the major causes of death worldwide. Thus, a more effective treatment approach is essential such as the inhibition of specific cancer-promoting molecules. Aurora kinases regulate the process of mitosis - a process of cell division that is necessary for normal cell proliferation. However, dysfunction of these kinases can contribute to cancer formation. The aberrant expression of Aurora kinases in lung cancer points to their crucial role in lung carcinogenesis. Therefore, understanding the fundamental functions as well as the cellular localization of Aurora kinases may contribute to evaluate their precise oncogenic function that will may lead to better specific targeting of these cancer-related molecules.  
  • 1.7K
  • 07 Jul 2021
Topic Review
Glycosylation of Cancer Extracellular Vesicles
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the tumor-associated glycans have already been identified in cancer EVs, which constitutes valuable sources of cancer biomarkers. Furthermore, glycans have also shown to play a role in EV protein sorting, uptake and tropism. Altogether, the EV glycan signatures hold tremendous potential to be applied into the clinical setting for both biomarker discovery and as therapeutic delivery systems.
  • 1.7K
  • 25 Jan 2021
Topic Review
Medicinal Plants with Anti-Leukemic Effects
Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient’s survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated.
  • 1.7K
  • 18 May 2021
Topic Review
Extracellular matrix in tumor microenvironment
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME.
  • 1.7K
  • 19 Jan 2021
Topic Review
Linking Obesity with Colorectal Cancer
The incidence of obesity and colorectal cancer (CRC) has risen rapidly in recent decades. More than 650 million obese and 2 billion overweight individuals are currently living in the world. CRC is the third most common cancer. Obesity is regarded as one of the key environmental risk factors for the pathogenesis of CRC. In the present review, we mainly focus on the epidemiology of obesity and CRC in the world, the United States, and China. We also summarize the molecular mechanisms linking obesity to CRC in different aspects, including nutriology, adipokines and hormones, inflammation, gut microbiota, and bile acids. The unmet medical needs for obesity-related CRC are still remarkable. Understanding the molecular basis of these associations will help develop novel therapeutic targets and approaches for the treatment of obesity-related CRC.
  • 1.7K
  • 14 Oct 2020
Topic Review
CCL21/CCR7 in Breast Cancer
Breast cancer is a leading cause of cancer-related deaths worldwide, predominantly caused by metastasis. It is generally accepted that the pattern of breast cancer metastasis is largely determined by the interaction between the chemokine receptors on cancer cells and the chemokines expressed at the sites of metastatic disease. Chemokine receptors belong to the G-protein-coupled receptors (GPCRs) family that appear to be implicated in inflammatory diseases, tumor growth and metastasis. One of its members, C-C Chemokine receptor 7 (CCR7), binds chemokines CCL19 and CCL21, which are important for tissue homeostasis, immune surveillance and tumorigenesis. These receptors have been shown to induce the pathobiology of breast cancer due to their ability to induce cellular proliferation and migration upon the binding of the cognate chemokine receptors. The underlying signaling pathways and exact cellular interactions within this biological system are not fully understood and need further insights.
  • 1.7K
  • 25 May 2021
Topic Review
Lynch Syndrome (LS)
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). 
  • 1.7K
  • 22 Aug 2023
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