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Topic Review
Chemotherapy Resistance of Ovarian Cancer
Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation.
  • 1.1K
  • 28 Nov 2022
Topic Review
Claudin-4 as Molecular Target for Epithelial Cancer Therapy
Claudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is overexpressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoter DNA), inflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acts as a barrier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown, clostridium perfringens enterotoxin (CPE), and C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. 
  • 1.1K
  • 25 May 2023
Topic Review
Treatment of Cisplatin/Platinum-Ineligible Metastatic Urothelial Carcinoma
Metastatic urothelial cancer (mUC) is an aggressive malignancy with limited treatment options. Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC). However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective therapy options. However, the combination of enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials.
  • 1.1K
  • 22 Mar 2024
Topic Review
Radiometal-Labeled Peptides in Cancer Diagnosis
Radiolabeled biomolecules targeted at tumor-specific enzymes, receptors, and transporters in cancer cells represent an intensively investigated and promising class of molecular tools for the cancer diagnosis and therapy. High specificity of such biomolecules is a prerequisite for the treatment with a lower burden to normal cells and for the effective and targeted imaging and diagnosis. The most impressive outputs in categories of newly developed structures, as well as imaging and diagnosis approaches, and the most intensively studied oncological diseases in this context, are emphasized in order to show future perspectives of radiometal labeled amino acid-based compounds in nuclear medicine.
  • 1.1K
  • 17 Mar 2021
Topic Review
Microbiota-Derived Butyrate in Colorectal Cancer
Butyrate is one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in colorectal cancer (CRC). Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.
  • 1.1K
  • 17 Mar 2022
Topic Review
Lithium as a Promising Anticancer Agent
Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development.
  • 1.1K
  • 23 Apr 2023
Topic Review
ADT Influence on Bone Health
Androgen-deprivation therapy (ADT) is a systemic therapy administered for the management of advanced prostate cancer (PCa). Although ADT may improve survival, long-term use reduces bone mass density (BMD), posing an increased risk of fracture. Considering the long natural history of PCa, it is essential to preserve bone health and quality-of-life in patients on long-term ADT. As an alternative to pharmacological interventions targeted at preserving BMD, current evidence recommends lifestyle modifications, including individualized exercise and nutritional interventions. Exercise interventions include resistance training, aerobic exercise, and weight-bearing impact exercise, and have shown efficacy in preserving BMD. At the same time, it is important to take into account that PCa is a progressive and debilitating disease in which a substantial proportion of patients on long-term ADT are older individuals who harbor axial bone metastases. Smoking cessation and limited alcohol consumption are commonly recommended lifestyle measures in patients receiving ADT. Contemporary guidelines regarding lifestyle modifications vary by country, organization, and expert opinion.
  • 1.1K
  • 18 Sep 2020
Topic Review
Melanoma Phenotypic Plasticity, Melanoma Cell Invasion and Metastasis
Melanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This is referred to as phenotype switching in melanoma, and it involves switching between quiescent and proliferative cell cycle states, and dramatic shifts in invasiveness, as well as changes in signaling pathways in the melanoma cells, and immune cell composition in the TME.
  • 1.1K
  • 02 Feb 2023
Topic Review
Berberine - Supportive Action Cancer
Berberine is very promising as the anticancer agent. Berberine not only possesses documented proapoptotic activity, which is in the focus of attention, but also seems to be a very important and promising compound in combined cancer treatment. Sensitization and elimination of drug resistance are very promising trends in the berberine research. What is more, berberine exhibits low toxicity towards healthy cells, which makes it safe for clinical use and proves its activity in biochemical disorders. 
  • 1.0K
  • 23 Nov 2020
Topic Review
Immunotherapeutic Treatments in Multiple Myeloma
Immunosuppression is a common feature of multiple myeloma (MM) patients and has been associated with disease evolution from its precursor stages. MM cells promote immunosuppressive effects due to both the secretion of soluble factors, which inhibit the function of immune effector cells, and the recruitment of immunosuppressive populations. Alterations in the expression of surface molecules are also responsible for immunosuppression.
  • 1.0K
  • 23 Jun 2021
Topic Review
Oncolytic Reovirus
Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent.
  • 1.0K
  • 09 Nov 2020
Topic Review
Drug Development Platform for Cholangiocarcinoma
Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains to be adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available
  • 1.0K
  • 09 Feb 2021
Topic Review
Colorectal Cancer Liver Metastases
Colorectal cancer (CRC) is a leading cause of death among cancer patients, and the liver is the most common visceral metastatic. Molecular cancer biomarkers are any measurable molecular indicator of the risk of cancer, the occurrence of cancer, or patient outcome, to help personalize treatment and to identify patients who may benefit most from a specific therapy. They may include germline or somatic genetic variants, epigenetic signatures, transcriptional changes, and proteomic signatures.
  • 1.0K
  • 21 Mar 2023
Topic Review
High-Grade Serous Ovarian Cancer
High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. 
  • 1.0K
  • 14 Feb 2024
Topic Review
Targeted Therapies in Advanced BTCs
Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas characterized by presentation with advanced disease and a poor prognosis. Chemotherapy is the mainstay of the current treatment that provides limited survival benefit, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. The present article provides an overview of a precision medicine centered evolving paradigm of BTC treatment.
  • 1.0K
  • 12 Aug 2020
Topic Review
Immunotherapy for Glioblastoma
       Glioblastoma (GBM) is the deadliest and most aggressive neuroepithelial cancer of the central nervous system (CNS) with an abysmal median survival of 14.6-month despite the multiple forms of intervention. In the United States, the total annual incidence rate of glioma has been ~6 cases per 100,000 individuals, of which GBM accounts for about 50% of the cases, with a higher predominance in males. Clinical studies have indicated that most of the GBM patients present an intact blood–brain barrier (BBB) for certain brain regions, capable of blocking the delivery of agents to cancer sites. The BBB is considered to prevent diffusion of 98% of small-molecule and 100% of large-molecule agents into the brain from blood circulation. Given the aggressive and heterogeneous nature of GBM and the blocking capability of BBB, a very limited number of medications for patients with GBM is available in clinics. In addition, due to the existence of other cellular and extracellular barriers, as well as the development of drug resistance over the treatment course, the efficacy of many current therapeutic approaches has been compromised.        Currently available standards of care for GBM include maximal tumor resection followed by radiotherapy, chemotherapy, and corticosteroids, all of which have immune suppressive characteristics. Unfortunately, complete surgical removal of the whole tumor is almost impossible due to their diffusive characteristics into normal brain tissue. Some reports indicated that ~65% of the post-surgery cases still showed residual tumor cells, which eventually contributed to a high relapse rate of GBM . Therefore, GBM patients may undergo repeated surgical resection, radiotherapy, chemotherapy, or additional bevacizumab treatment. Eventually, most of the patients suffering from GBM will relapse despite an ample set of interventional approaches. According to the data from Surveillance and Epidemiology, the median overall survival (OS) of GBM patients was normally less than 2 years from the time of first progression or relapse. An international phase III randomized trial, conducted by the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC), has shown that the median OS of GBM patients who received radiotherapy and Temozolomide therapy remains poor (14.6 months). Moreover, Grossman and colleagues found that the utilization of systemic chemotherapy and hyperfractionated radiation therapy with corticosteroids is likely to disable immune activity. Immune-suppressive characteristics, high toxicity, and lower OS of traditional care made a considerable number of GBM patients (~50%) not accept any second-line of anti-tumor treatment. In addition, there is no evidence that traditional intervention can significantly impact the OS rate under a recurrence setting. Accordingly, given the poor prognosis and limited therapy regimens for patients affected by GBM, there is an urgent need to develop novel therapeutic approaches.
  • 1.0K
  • 25 Aug 2020
Topic Review
Chronic Myeloid Neoplasms
Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. 
  • 1.0K
  • 29 Apr 2021
Topic Review
ICIs for HCC treatment
Immunotherapies are promising approaches for treating hepatocellular carcinomas (HCCs) refractory to conventional therapies. However, a recent clinical trial of immune checkpoint inhibitors (ICIs) revealed that anti-tumor responses to ICIs are not satisfactory in HCC cases. Therefore, it is critical to identify molecular markers to predict outcome and develop novel combination therapies that enhance the efficacy of ICIs. Recently, several attempts have been made to classify HCC based on genome, epigenome, and transcriptome analyses. These molecular classifications are characterized by unique clinical and histological features of HCC, as well immune phenotype. For example, HCCs exhibiting gene expression patterns with proliferation signals and stem cell markers are associated with the enrichment of immune infiltrates in tumors, suggesting immune-proficient characteristics for this type of HCC. However, the presence of activating mutations in β-catenin represents a lack of immune infiltrates and refractoriness to ICIs. Although the precise mechanism that links the immunological phenotype with molecular features remains controversial, it is conceivable that alterations of oncogenic cellular signaling in cancer may lead to the expression of immune-regulatory molecules and result in the acquisition of specific immunological microenvironments for each case of HCC. Therefore, these molecular and immune characteristics should be considered for the management of HCC using immunotherapy.
  • 1.0K
  • 02 Nov 2020
Topic Review
Bone in Inherited Endocrine Tumors
Endocrine tumors are neoplasms originating from specialized hormone-secreting cells. They can develop as sporadic tumors, caused by somatic mutations, or in the context of familial Mendelian inherited diseases. Congenital forms, manifesting as syndromic or non-syndromic diseases, are caused by germinal heterozygote autosomal dominant mutations in oncogenes or tumor suppressor genes.
  • 1.0K
  • 30 Aug 2021
Topic Review
Clinical Perspective of Liquid Biopsy
The term liquid biopsy (LB) refers to the study of circulating tumor cells, circulating tumors nucleic acids free of cells or contained in exosomes, and information about platelets associated with tumors. LB can be performed in different biofluids and allows the limitations of tissue biopsy to be overcome offering possibilities of tumor identification reflecting in real time tumor heterogeneity. In addition, LB allows screening and early detection of cancer, real-time monitoring of therapy, stratification and therapeutic intervention, a therapeutic target and resistance mechanism, and a risk of metastatic relapse. 
  • 1.0K
  • 22 Oct 2021
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