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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).
  • 620
  • 02 Jun 2022
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.
  • 620
  • 27 Sep 2022
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).
  • 619
  • 19 Apr 2022
Topic Review
Metabolic rewiring in glioblastoma microenvironment
Brain cancer cells exist with the glial cells in a functional syncytium based on a continuous metabolic rewiring, which supports the tumor growth. Standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment and this may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution. Bioinformatic and computational studies help to disengage the complexity of the metabolism in modules. Based on the literature findings, we identified eight main metabolic modules that can be considered during the disease progression, and their fluxes could be integrated to establish targeted time-dependent therapies.
  • 616
  • 06 Apr 2021
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.
  • 616
  • 16 Jan 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.
  • 616
  • 07 Feb 2023
Topic Review
Claudin in Gastric Cancer
An analysis of claudin proteins has proposed the subdivision of the claudin family into ‘classic’ and ‘non-classic’ groups, according to the alternative splicing of the CLDN18 gene exons, and the classic (CLDNs 1–10, CLDN14, CLDN15, CLDN17, CLDN19) and non-classic types (CLDN 11–13, CLDN16, CLDN18, and CLDNs 20–24).
  • 616
  • 27 Feb 2024
Topic Review
Perioperative Tailored Treatments for Gastric Cancer
Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. The half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery).
  • 616
  • 09 Mar 2023
Topic Review
Treatment Algorithm in Cancer-Associated Thrombosis
Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications.
  • 615
  • 04 Jan 2022
Topic Review
Inadequate Treatment Evidence for BRCA-Positive Male Breast Cancer
Male breast cancer (MBC) is an orphan disease that is on the rise but remains understudied. Mutations in genes sensitive to DNA damage response, BRCA1 and BRCA2, are strongly implicated in MBC development. Evidence-based guidance for the treatment of MBC that have BRCA mutations is lacking with most published data arising from retrospective or case studies with small patient cohorts. There is a growing understanding that male and female BCs are distinct diseases with different clinicopathological and molecular characteristics. Despite extensive advancements in other BRCA-positive malignancies, there remains a striking unmet need for dedicated research for BRCA-related MBC to better understand and optimise clinical management for this subgroup of patients. Such studies are imperative to circumvent the scant information available currently to provide optimal screening and treatment strategies that are tailored for BRCA-positive MBC patients.
  • 615
  • 22 Jul 2022
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. 
  • 615
  • 29 May 2023
Topic Review
Breast Cancer Metastases Development
Breast cancer is one of the main causes of morbidity and mortality in women. Early breast cancer has a relatively good prognosis, in contrast to metastatic disease with rather poor outcomes. Metastasis formation in distant organs is a complex process requiring cooperation of numerous cells, growth factors, cytokines, and chemokines. Tumor growth, invasion, and finally systemic spread are driven by processes of angiogenesis, vasculogenesis, chemotaxis, and coagulation.
  • 615
  • 15 Feb 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.
  • 614
  • 26 Jul 2022
Topic Review
Lung Cancer Screening with Low-Dose CT in Europe
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. 
  • 614
  • 07 Aug 2023
Topic Review
Immunotherapy and Radiotherapy
Immunotherapy, the modern oncological treatment with immune checkpoint inhibitors (ICIs), has been part of the clinical practice for malignant melanoma for more than a decade. Anti-cytotoxic T-lymphocyte antigen 4 (CTLA4), anti-programmed cell death Protein 1 (PD-1), or anti programmed death-ligand 1 (PD-L1) agents are currently part of the therapeutic arsenal of metastatic or relapsed disease in numerous cancers; more recently, they have also been evaluated and validated as consolidation therapy in the advanced local stage. The combination with radiotherapy, a treatment historically considered loco-regional, changes the paradigm, offering—via synergistic effects—the potential to increase immune-mediated tumor destruction.
  • 613
  • 21 Nov 2022
Topic Review
Oncometabolites in Peritoneal Cancers and Precision Cancer Medicine
Peritoneal cancers, encompassing both primary peritoneal cancers and secondary peritoneal metastases, present significant clinical challenges due to their aggressive nature and generally poor prognosis. Primary peritoneal cancers, such as peritoneal mesothelioma and primary peritoneal carcinoma, arise directly in the peritoneal cavity, while secondary peritoneal cancers result from the spread of cancer from other organs to the peritoneum. Understanding the role of cancer cell metabolism and cancer-promoting metabolites in peritoneal cancers can provide new insights into the mechanisms that drive tumor progression and can identify novel therapeutic targets and biomarkers for early detection, prognosis, and treatment response. Cancer cells dynamically reprogram their metabolism to facilitate tumor growth and overcome metabolic stress, with cancer-promoting metabolites such as kynurenine, lactate, and sphingosine-1-phosphate promoting cell proliferation, angiogenesis, and immune evasion.Targeting cancer-promoting metabolites and inhibiting the production or function of these metabolites could disrupt the metabolic pathways that contribute to tumor growth and progression. This approach could also lead to the development of effective combinatorial and adjuvant therapies for peritoneal cancers. With the observed metabolomic heterogeneity in cancer patients, defining peritoneal cancer metabolome and cancer-promoting metabolites holds great promise for improving patient outcomes by enabling personalized treatment approaches based on an individual's metabolic profile.
  • 613
  • 22 May 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.
  • 612
  • 30 Mar 2021
Topic Review
Cell-Cell Junctions in Oesophageal Squamous Cell Carcinoma
Cell–cell junctions comprise various structures, including adherens junctions, tight junctions, desmosomes, and gap junctions. They link cells to each other in tissues and regulate tissue homeostasis in critical cellular processes. Recent advances in cell–cell junction research have led to critical discoveries. Cell–cell adhesion components are important for the invasion and metastasis of tumour cells, which are not only related to cell–cell adhesion changes, but they are also involved in critical molecular signal pathways. They are of great significance, especially given that relevant molecular mechanisms are being discovered, there are an increasing number of emerging biomarkers, targeted therapies are becoming a future therapeutic concern, and there is an increased number of therapeutic agents undergoing clinical trials. Oesophageal squamous cell carcinoma (ESCC), the most common histological subtype of oesophageal cancer, is one of the most common cancers to affect epithelial tissue. ESCC progression is accompanied by the abnormal expression or localisation of components at cell–cell junctions.
  • 612
  • 18 Oct 2022
Topic Review
Immunotherapies Targeting the Tumour Microenvironment
Brain tumour malignancies, especially glioblastoma multiform (GBM), characteristically reflect an abysmal disease prognosis with high mortality rates in both adult and paediatric populations. In adults, GBM is the most common and aggressive primary brain tumour, accounting for 15% of central nervous system (CNS) tumours, and 50.1% of malignancies, representing the most frequent form of primary malignant brain tumour. 
  • 612
  • 19 Sep 2023
Topic Review
Metastatic Breast Cancer: Cytopathology Combined with Molecular Analysis
Metastatic breast cancer (MBC) remains in most cases an incurable disease with genetic complexity and heterogeneity. Improvements in classification and management have been introduced, in addition to the development of endocrine and anti-HER2 targeted therapies. Cytological material can be processed for ancillary testing for diagnostic and therapeutic purposes. Reassessment of receptor status is indicated due to changes in tumor biology and metastatic presentation. Program Death Ligand-1 (PD-L1) expression is the only approved biomarker for predicting immune checkpoint inhibitor response in metastatic TNBC, evaluated by immunostaining. The feasibility of applying PD-L1 assays in MBC cytological samples can be recommended, with the adoption of a combined positive score. Non-formalin cytological samples provide higher purity, cellular yield, and better tumor fraction for single-multi gene assays. In MBC, molecular tests enable personalized therapy such as PIK3CA, NTRK fusion genes, and microsatellite instability (MSI). Cytopathology combined with molecular analysis must be performed effectively in routine clinical practice, through procedure standardization and experience dissemination.
  • 612
  • 30 Dec 2022
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