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Topic Review
Mechanisms of Immune-Checkpoint Blockade Resistance and Cancer Epigenetics
Tumor evolution to evade immune surveillance is a hallmark of carcinogenesis, and the modulation of tumor immunogenicity has been a challenge to present therapeutic responses in immunotherapies alone for numerous cancers. By altering the cell phenotype and reshaping the tumor microenvironment, epigenetic modifications enable tumor cells to overcome immune surveillance as a mechanism of cancer progression and immunotherapy resistance. Immune-checkpoint blockade (ICB) therapies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4/CD152), programmed cell death protein 1 (PD-1/CD279), and programmed death-ligand 1 (PD-L1) have presented unprecedented responses in significant percentages of cancer patients. Even then, efficacy and response rates vary according to cancer types and particular ICB regimens. Researchers have therefore since attempted to find ways to optimize immunotherapy and overcome immune checkpoint inhibitor resistance.
  • 674
  • 02 Mar 2023
Topic Review
Exploiting N803 for Effective Immunotherapy of Solid Malignancies
Identifying effective immunotherapies for solid tumors remains challenging despite the significant clinical responses observed in subsets of patients treated with immune checkpoint inhibitors. Interleukin-15 (IL-15) is a promising cytokine for the treatment of cancer as it stimulates NK and CD8+ lymphocytes. However, unfavorable pharmacokinetics and safety concerns render recombinant IL-15 (rIL-15) a less attractive modality. These shortcomings were addressed by the clinical development of heterodimeric IL-15 agonists, including N803.
  • 674
  • 03 Jul 2023
Topic Review
Immunotherapy in Bladder Cancer
Urinary bladder cancer is one of the most important cancers of the urinary-sex system, causing high morbidity and mortality in many patients. Various methods of treating this type of cancer have been developed over the years. The most popular is the highly effective method using Bacillus Calmette-Guerin, which has an effective effect on a large percentage of patients. However, due to the genetic instability of bladder cancer and the individual needs of patients, different methods of treatment are being sought. Immunological control points are molecules on the surface of the cell that affect the immune response and reduce the strength of the immune response. Among these checkpoints, PD-1 inhibitors (the protein that is programmed to kill cell-1) /PD-L1 (the ligand of the protein that is programmed to kill cell 1) are intended to block these molecules, resulting in activation of T cells, and bladder cancer have been described as the use of atezolizumab, awelumab, durwalumab, niwolumab and pembrolizumab. The inhibition of another key immunological control point, CTLA-4 (cytotoxic T-lymphocyte antigen), may result in mobilisation of the immune system against bladder cancer, and anti-CTLA-4 antibodies discussed the use of Ipilimumab and Tremelimumab. In addition, there are several different approaches to the effective treatment of bladder cancer, such as the use of ganciclovir kinase inhibitors and mTOR (mammalian rapamycin target), IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). Genetic therapy and disruption of different signal paths are currently being studied. Studies suggest that combining several methods increases the efficacy of treatment and positive results in the patient. 
  • 673
  • 20 Jan 2021
Topic Review
Translational Immuno-Oncology Research with Organoids
As the complexity of tumour microenvironment (TME) has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types. Here, the researchers discuss how organoids can study the TME across cancers and how these features may improve precision I/O. 
  • 673
  • 25 Apr 2023
Topic Review
Pancreatic Ductal Adenocarcinoma Stroma in Photodynamic Therapy
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour–stromal cell interactions. So far, the pre-clinical studies have suggested that photodynamic therapy (PDT) can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. 
  • 673
  • 01 Sep 2023
Topic Review
Treatment of BRAF-Mutant Melanoma
Melanoma is the most lethal form of skin cancer. Melanoma is usually curable with surgery if detected early, however, treatment options for patients with metastatic melanoma are limited and the five-year survival rate for metastatic melanoma had been 15–20% before the advent of immunotherapy. Treatment with immune checkpoint inhibitors has increased long-term survival outcomes in patients with advanced melanoma to as high as 50% although individual response can vary greatly. A mutation within the MAPK pathway leads to uncontrollable growth and ultimately develops into cancer. The most common driver mutation that leads to this characteristic overactivation in the MAPK pathway is the B-RAF mutation. Current combinations of BRAF and MEK inhibitors that have demonstrated improved patient outcomes include dabrafenib with trametinib, vemurafenib with cobimetinib or encorafenib with binimetinib. Treatment with BRAF and MEK inhibitors has met challenges as patient responses began to drop due to the development of resistance to these inhibitors which paved the way for development of immunotherapies and other small molecule inhibitor approaches to address this. Resistance to these inhibitors continues to push the need to expand our understanding of novel mechanisms of resistance associated with treatment therapies.
  • 672
  • 21 Jun 2021
Topic Review
Physical Activity and Cancer Care
Cancer treatments cause numerous side effects and have a negative impact on all body systems. Physical activity is important for cancer patients.
  • 672
  • 31 Aug 2022
Topic Review
Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury
Cisplatin, a potent chemotherapeutic agent, is marred by severe nephrotoxicity that is governed by mechanisms involving oxidative stress, inflammation, and apoptosis pathways. The transcription factor Nrf2, pivotal in cellular defense against oxidative stress and inflammation, is the master regulator of the antioxidant response, upregulating antioxidants and cytoprotective genes under oxidative stress.
  • 672
  • 12 Sep 2023
Topic Review
Micro-Fragmented Adipose Tissue for Targeted Drug Delivery
Major limitations in the effective treatment of neurological cancer include systemic cytotoxicity of chemotherapy, inaccessibility, and inoperability. The capability to successfully target a drug to the tumor site(s) without incurring serious side effects—especially in the case of aggressive tumors, such as glioblastoma and neuroblastoma—would represent a significant breakthrough in therapy. Orthotopic systems, capable of storing and releasing proteins over a prolonged period at the site of a tumor, that utilize nanoparticles, liposomes, and hydrogels have been proposed. One candidate for drug delivery is Micro-Fragmented Adipose Tissue (MFAT). Easily obtained from the patient by abdominal subcutaneous liposuction (autologous), and with a high content of Mesenchymal Stem Cells (MSCs), mechanically derived nanofat is a natural tissue graft with a structural scaffold organization. It has a well-preserved stromal vascular fraction and a prolonged capacity to secrete anti-tumorigenic concentrations of pre-absorbed chemotherapeutics within extracellular vesicles. 
  • 672
  • 15 Sep 2023
Topic Review
Biology and Development of DNA-Targeted Drugs for Cancer
DNA-targeted drugs constitute a specialized category of pharmaceuticals developed for cancer treatment, directly influencing various cellular processes involving DNA. These drugs aim to enhance treatment efficacy and minimize side effects by specifically targeting molecules or pathways crucial to cancer growth. Unlike conventional chemotherapeutic drugs, discoveries have yielded DNA-targeted agents with improved effectiveness, and a new generation is anticipated to be even more specific and potent. The sequencing of the human genome in 2001 marked a transformative milestone, contributing significantly to the advancement of targeted therapy and precision medicine. Anticipated progress in precision medicine is closely tied to the continuous development in the exploration of synthetic lethality, DNA repair, and expression regulatory mechanisms, including epigenetic modifications. The integration of technologies like circulating tumor DNA (ctDNA) analysis further enhances our ability to elucidate crucial regulatory factors, promising a more effective era of precision medicine. The combination of genomic knowledge and technological progress has led to a surge in clinical trials focusing on precision medicine. These trials utilize biomarkers for identifying genetic alterations, molecular profiling for potential therapeutic targets, and tailored cancer treatments addressing multiple genetic changes. The evolving landscape of genomics has prompted a paradigm shift from tumor-centric to individualized, genome-directed treatments based on biomarker analysis for each patient.
  • 671
  • 09 Jan 2024
Topic Review
Melanoma Tumor-Associated Macrophages
TAMs constitute a large fraction of infiltrating immune cells in melanoma tissues, but their significance for clinical outcomes remains unclear. Secretory phenotype, but not TAM density, size, location, nor CD11c/CD209 subsets polarity, correlates with patient survival.
  • 671
  • 08 Oct 2021
Topic Review
CAR NK Cell Therapy for Metastatic Melanoma
Melanoma is among the most lethal forms of cancer, accounting for 80% of deaths despite comprising just 5% of skin cancer cases. Treatment options remain limited due to the genetic and epigenetic mechanisms associated with melanoma heterogeneity that underlie the rapid development of secondary drug resistance. For this reason, the development of novel treatments remains paramount to the improvement of patient outcomes. Although the advent of chimeric antigen receptor-expressing T (CAR-T) cell immunotherapies has led to many clinical successes for hematological malignancies, these treatments are limited in their utility by their immune-induced side effects and a high risk of systemic toxicities. CAR natural killer (CAR-NK) cell immunotherapies are a particularly promising alternative to CAR-T cell immunotherapies, as they offer a more favorable safety profile and have the capacity for fine-tuned cytotoxic activity. 
  • 671
  • 06 Dec 2023
Topic Review
Notch and HCC
The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection.
  • 670
  • 22 Apr 2021
Topic Review
Proton Therapy for PBI
Partial breast irradiation (PBI) presents an opportunity to improve quality of life during treatment with a significantly shorter treatment duration. By targeting less non-target breast tissue, excess radiation exposure and resulting toxicities are also reduced. Proton therapy represents a precision radiotherapy technology that builds on these advantages by further limiting the normal tissue exposure to unnecessary radiation dose not only to uninvolved breast tissue but also the underlying thoracic organs including the heart and lungs. 
  • 670
  • 23 Jun 2021
Topic Review
Scalp Cooling
Chemotherapy-induced alopecia (CIA), a side effect with high impact, can be prevented by cooling the scalp during the administration of some cytotoxic drugs. Scalp cooling is a well-known method to try to prevent CIA during the administration of cytotoxic drugs for solid tumors. Using scalp cooling, liquid refrigerant is pumped as coolant through a cooling cap that is placed on the head of the patient. In general, scalp cooling is started 20–45 min prior to, during, and up to 20–150 min after the chemotherapy infusion.
  • 670
  • 20 Aug 2021
Topic Review
Health-Related Quality of Life in Neuroendocrine Tumors
Neuroendocrine tumors (NETs) are a group of heterogenous neoplasms arising from the diffuse neuroendocrine system. Several therapies have been added to the treatment landscape that have improved long-term outcomes. Despite therapeutic advancements, the symptom burden of the disease remains high, impacting health-related quality of life (HRQoL). 
  • 670
  • 29 Apr 2022
Topic Review
Cancer Stem Cell Relationship with Pro-Tumoral Inflammatory Microenvironment
Cancer stem cells (CSCs)  are capable of altering their own properties in a variety of ways to preserve their stem cell phenotype, resist different therapies, and evade the immune system’s anti-tumor attack. Through immune escape mechanisms, they are not only able to hide themselves from the immune system but also to influence the anti-tumor immune elimination mechanisms in a way that is favorable to them. By manipulating their own capabilities, CSCs have the potential to develop entirely novel anti-cancer treatments and methods to prevent disease recurrence. It is clear that there is an intense and complex multi-level relationship between the tumor microenvironment (TME) and CSCs. CSCs are able to develop an inflammatory niche that allows them to persist and divide on their own. They maintain an intense relationship with the cellular elements of the TME, reprogramming them into cells for the survival and proliferation of CSCs. In turn, the reprogrammed TME cells enhance the survival and proliferation of CSCs and thereby facilitate their own survival and function.
  • 670
  • 20 Jan 2023
Topic Review
Drug Delivery Methods in Childhood Brain Tumors
Only four drugs have been licensed globally for brain tumors. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. This drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. 
  • 670
  • 13 Mar 2023
Topic Review
Bioinformatics Analysis and Genetic Technologies for Glioblastoma Multiforme
As the most malignant primary brain tumor in adults, a diagnosis of glioblastoma multiforme (GBM) continues to carry a poor prognosis. GBM is characterized by cytoprotective homeostatic processes such as the activation of autophagy, capability to confer therapeutic resistance, evasion of apoptosis, and survival strategy even in the hypoxic and nutrient-deprived tumor microenvironment. The gold standard of therapy, which involves radiotherapy and concomitant and adjuvant chemotherapy with temozolomide (TMZ), has been a game-changer for patients with GBM, relatively improving both overall survival (OS) and progression-free survival (PFS); however, TMZ is now well-known to upregulate undesirable cytoprotective autophagy, limiting its therapeutic efficacy for induction of apoptosis in GBM cells. The identification of targets utilizing bioinformatics-driven approaches, advancement of modern molecular biology technologies such as clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein (Cas9) or CRISPR-Cas9 genome editing, and usage of microRNA (miRNA)-mediated regulation of gene expression led to the selection of many novel targets for new therapeutic development and the creation of promising combination therapies.
  • 669
  • 07 Apr 2023
Topic Review
Glutathione S-Transferase Mu 5
Our previous study demonstrated that the glutathione S-transferase Mu 5 (GSTM5) gene is highly CpG-methylated in bladder cancer cells and that demethylation by 5-aza-dC activates GSTM5 gene expression. The aim of the present study was to investigate the role of GSTM5 in bladder cancer.
  • 668
  • 01 Apr 2021
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