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Topic Review
Nanocarrier-Based Codelivery of Chemotherapeutic Agent with Phytochemicals
Anticancer drugs in monotherapy are ineffective to treat various kinds of cancer due to the heterogeneous nature of cancer. Moreover, available anticancer drugs possessed various hurdles, such as drug resistance, insensitivity of cancer cells to drugs, adverse effects and patient inconveniences. Hence, plant-based phytochemicals could be a better substitute for conventional chemotherapy for treatment of cancer due to various properties: lesser adverse effects, action via multiple pathways, economical, etc. Various preclinical studies have demonstrated that a combination of phytochemicals with conventional anticancer drugs is more efficacious than phytochemicals individually to treat cancer because plant-derived compounds have lower anticancer efficacy than conventional anticancer drugs. Moreover, phytochemicals suffer from poor aqueous solubility and reduced bioavailability, which must be resolved for efficacious treatment of cancer.
  • 615
  • 16 Mar 2023
Topic Review
ROS1 for Advanced Non Small Cell Lung Cancer
ROS proto-oncogene 1 (ROS1) rearrangements occur in 0.9–2.6% of patients with non small cell lung cancer (NSCLC), conferring sensitivity to treatment with specific tyrosine-kinase inhibitors (TKI). Crizotinib, a first-generation TKI, was the first target-therapy approved for the first-line treatment of ROS1-positive NSCLC. Entrectinib, a multitarget inhibitor with an anti-ROS1 activity 40 times more potent than crizotinib and better activity on the central nervous system (CNS), received approval for treatment-naive patients. 
  • 615
  • 27 Jul 2023
Topic Review
Oncogenic Pathways and Immune Microenvironment
Oncogenic signals affect the expression of several immune-related molecules, including immune regulatory receptors, ligands, growth factors and other humoral factors, which affect diverse stromal cells as well as cancer cells. The cellular components of tumors and their states are major players in the regulation of the tumor immune microenvironment.
  • 614
  • 12 Oct 2021
Topic Review
Mutation Profile of Myelofibrosis
Myelofibrosis refers to fibrosis in the bone marrow associated with certain bone marrow cancers. It is a characteristic of primary myelofibrosis and may develop later in other bone marrow cancers with overproduction of blood cells, such as polycythemia vera and essential thrombocythemia. It has been confirmed that mutations in three key genes, Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia oncogene (MPL), can increase the activity of blood-producing cells, make them grow more actively, and are associated with the development of myelofibrosis. Approximately 80% of myelofibrosis cases carry additional mutations that often involve proteins that control how genes are turned on and off. The presence of mutations provides evidence of a cancerous process. The order in which these mutations occur can influence how the disease manifests. Studies have shown that fibrosis is secondary to the cancerous process and is closely linked to abnormal cell growth driven by mutations.
  • 614
  • 20 Feb 2024
Topic Review
MicroRNA-21 Regulates Stemness in PDAC
Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer (PCa) with a low survival rate. microRNAs (miRs) are endogenous, non-coding RNAs that moderate numerous biological processes. miRs have been associated with the chemoresistance and metastasis of PDAC and the presence of a subpopulation of highly plastic “stem”-like cells within the tumor, known as cancer stem cells (CSCs).
  • 613
  • 19 Apr 2022
Topic Review
Management of Immunotherapy-Related Toxicity in Genitourinary Cancers
Genitourinary (GU) malignancies are among the most common types of cancer. The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs).
  • 612
  • 02 Jun 2022
Topic Review
Autocrine IGF-II-Associated Cancers
The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IRA) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy.
  • 612
  • 08 Mar 2024
Topic Review
Biomarkers in Chondrosarcoma
Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2, COL2A1, and PD-L1. In addition, several molecule-targeting agents and immunotherapy have shown favorable antitumor activities in clinical studies of patients with advanced chondrosarcoma.
  • 611
  • 10 Feb 2022
Topic Review
Obesity-Associated Extracellular Matrix Remodeling
Accumulated evidence has demonstrated that adipocytes can transform or de-differentiate into myofibroblast/fibroblast-like cells, which play vital roles in obesity-related extracellular matrix (ECM) remodeling and cancer progression. Adipose tissue, an energy storage and endocrine organ, is emerging as an essential player for ECM remodeling. Fibrosis is one of the hallmarks of obese adipose tissue, featuring excessive ECM deposition and enhanced collagen alignment. A variety of ECM components and ECM-related enzymes are produced by adipocytes and myofibroblasts in obese adipose tissue.
  • 611
  • 16 Jan 2023
Topic Review
Cannabinoids as Modulators of Nrf2 Pathway
The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2.
  • 611
  • 15 Dec 2023
Topic Review
PET and SPECT Imaging in Prostate Cancer
The current state of Targeted Alpha Therapy (TAT) in prostate cancer, particularly in mCRPCT (metastatic castration-resistant prostate cancer). The widely used Radium-223 and the novel trend in the TAT field with a special focus on prostate-specific membrane antigen (PSMA)-based alpha therapy.
  • 610
  • 07 Feb 2023
Topic Review
Targeted Therapies in Small Cell Lung Cancer
Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumour accounting for 15% of lung malignant neoplasms. SCLC has been considered “a graveyard for drug development” for a long time, with chemotherapy still representing the standard treatment across different lines of therapy. Differently from NSCLC, identifying actionable targets in SCLC has been challenging, also because most common molecular alterations regard either TP53 or RB1 genes that are currently considered pharmacologically untargetable. Several attempts have been made in the past with clinical trials investigating tailored inhibitors against different potential targets, such as mTOR, cKIT, MET, BCL-2, etc., overall failing to show any sign of activity in SCLC patients. 
  • 610
  • 29 May 2023
Topic Review
Two Complementarity Immunotherapeutics in NSCLC
The idea of using two different immunotherapies in cancer patients is based on the attempt to stimulate or inhibit different immune cells at different levels of their activity (e.g., in the lymph node and in the tumour). The most commonly used combination immunotherapy involves antibodies that target molecules capable of stimulation of the activity of lymphocytes and other immune cells and molecules that are able to inhibit this activity. Another combination immunotherapy method is the use of immune checkpoint inhibitors in combination with agents that modify the tumour microenvironment in a non-specific manner (e.g., pro-inflammatory cytokines, immunosuppressive cytokine inhibitors, and indoleamine 2,3-dioxygenase and adenosine inhibitors).
  • 609
  • 24 Jun 2021
Topic Review
Molecular Biology of Soft Tissue Sarcomas
Soft tissue sarcomas comprise all malignant tumors that develop from soft tissues in the body and that are thought to derive from a mesenchymal origin. They are mostly rare tumors and characterized by a large clinical and biological heterogeneity, with more than 100 different subtypes in the latest WHO classification. Their management is therefore complex and historically based on histological characteristics, but it has been transformed by the help of molecular biology for diagnosis and treatment.
  • 609
  • 28 May 2022
Topic Review
Immunotherapy in Advanced Biliary Tract Cancers
Biliary tract cancers (BTC) are a heterogeneous group of rare but highly lethal carcinomas that originate from the gallbladder, intrahepatic bile ducts, and extrahepatic (perihilar and distal) bile ducts. Cholangiocarcinoma (CCA), or cancer arising from the bile ducts, accounts for 3% of all gastrointestinal malignancies and is the second most common primary liver cancer after hepatocellular carcinoma (HCC). Incidence of CCA varies greatly by geographic region, with the highest rates observed in Southeast Asia, including Thailand, where cases are as high as 113 per 100,000 in men and 50 per 100,000 women.
  • 609
  • 26 Jul 2022
Topic Review
CD133 as a Functional Unit in Glioblastoma
Biomarkers for resistance in Glioblastoma multiforme (GBM) are lacking, and progress in the clinic has been slow to arrive. CD133 (prominin-1) is a membrane-bound glycoprotein on the surface of cancer stem cells (CSCs) that has been associated with poor prognosis, therapy resistance, and tumor recurrence in GBM. Due to its connection to CSCs, to which tumor resistance and recurrence have been partially attributed in GBM, there is a growing field of research revolving around the potential role of CD133 in each of these processes. However, despite encouraging results in vitro and in vivo, the biological interplay of CD133 with these components is still unclear, causing a lack of clinical application. In parallel, omic data from biospecimens that include CD133 are beginning to emerge, increasing the importance of understanding CD133 for the effective use of these highly dimensional data sets. Given the significant mechanistic overlap, prioritization of the most robust findings is necessary to optimize the transition of CD133 to clinical applications using patient-derived biospecimens. 
  • 609
  • 22 Sep 2023
Topic Review
Venetoclax and Hypomethylating Agent Combination in Myeloid Malignancies
There has been a widespread adoption of hypomethylating agents (HMA: 5-Azacytidine (5-Aza)/decitabine) and venetoclax (Ven) for the treatment of acute myeloid leukemia (AML); however, the mechanisms behind the combination’s synergy are poorly understood. Monotherapy often encounters resistance, leading to suboptimal outcomes; however, the combination of HMA and Ven has demonstrated substantial improvements in treatment responses.
  • 609
  • 26 Feb 2024
Topic Review
Gender Differences in Cardio-Oncology
Gender differences exist throughout the medical field and significant progress has been made in understanding the effects of gender in many aspects of healthcare. The field of cardio-oncology is diverse and dynamic with new oncologic and cardiovascular therapies approved each year; however, there is limited knowledge regarding the effects of gender within cardio-oncology, particularly the impact of gender on cardiotoxicities. The relationship between gender and cardio-oncology is unique in that gender likely affects not only the biological underpinnings of cancer susceptibility, but also the response to both oncologic and cardiovascular therapies. Furthermore, gender has significant socioeconomic and psychosocial implications which may impact cancer and cardiovascular risk factor profiles, cancer susceptibility, and the delivery of healthcare.
  • 608
  • 27 Sep 2022
Topic Review
Genetic Characteristics and Peculiarities of the isPMRCC
Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC.
  • 608
  • 29 Nov 2023
Topic Review
Preclinical Evaluation of 99mTc-ZHER2
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.
  • 607
  • 30 Mar 2021
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