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REV-ERB receptors are members of the nuclear receptor superfamily of proteins, which act as both intracellular receptors and transcription factors, therefore modulating the expression of target genes. REV-ERBs act as transcription repressors because of their unique structure. Their predominant role involves the control of peripheral circadian rhythmicity by participating in a transcription-translation feedback loop with other major clock genes. Regarding their role in cancer pathogenesis, recent studies in various cancerous tissues have revealed that their expression was downregulated in the majority of the cases. Dysregulation of their expression was also implicated in cancer-associated cachexia. The pharmacological restoration of their effects is feasible with synthetic agonists, which have been explored in preclinical studies but with scarce data. There is a need for further investigation, primarily with mechanistic studies, on the effect of the REV-ERB-induced circadian rhythm deregulation in carcinogenesis and cancer-related systemic effects, such as cachexia, in order to address the potential of relevant therapeutic implications.
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Caquexia , Neoplasias , Humanos , Caquexia/genética , Fatores de Transcrição , Ritmo Circadiano/genética , Receptores Citoplasmáticos e Nucleares/genética , Neoplasias/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismoRESUMO
Benign metastasizing leiomyoma is a metastasizing form of leiomyoma, which is a benign uterine tumor that typically affects women of reproductive age. A hysterectomy is typically performed 10-15 years before the disease's metastatic progression. We present a case of a postmenopausal woman who presented to the emergency department with worsening dyspnea and a history of hysterectomy due to leiomyoma. A computed tomography scan of the chest revealed diffuse bilateral lesions. An open-lung biopsy was performed, and the lung lesions were found to have leiomyoma cells. The patient began letrozole treatment and showed clinical improvement without any serious adverse events.
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Leiomioma , Neoplasias Pulmonares , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Pulmonares/patologia , Leiomioma/patologia , Neoplasias Uterinas/patologia , Pulmão/patologia , Tomografia Computadorizada por Raios XRESUMO
Background: Cardiac injury (CI) is not a rare condition among hospitalized patients with coronavirus disease 2019 (COVID-19). Its prognostic value has been extensively reported through the literature, mainly in the context of observational studies. An impressive number of relevant meta-analyses has been conducted. These meta-analyses present similar and consistent results; yet interesting methodological issues emerge. Methods: A systematic literature search was conducted aiming to identify all relevant meta-analyses on (i) the incidence, and (ii) the prognostic value of CI among hospitalized patients with COVID-19. Results: Among 118 articles initially retrieved, 73 fulfilled the inclusion criteria and were included in the systematic review. Various criteria were used for CI definition mainly based on elevated cardiac biomarkers levels. The most frequently used biomarker was troponin. 30 meta-analyses reported the pooled incidence of CI in hospitalized patients with COVID-19 that varies from 5% to 37%. 32 meta-analyses reported on the association of CI with COVID-19 infection severity, with only 6 of them failing to show a statistically significant association. Finally, 46 meta-analyses investigated the association of CI with mortality and showed that patients with COVID-19 with CI had increased risk for worse prognosis. Four meta-analyses reported pooled adjusted hazard ratios for death in patients with COVID-19 and CI vs those without CI ranging from 1.5 to 3. Conclusions: The impact of CI on the prognosis of hospitalized patients with COVID-19 has gained great interest during the pandemic. Methodological issues such as the inclusion of not peer-reviewed studies, the inclusion of potentially overlapping populations or the inclusion of studies with unadjusted analyses for confounders should be taken into consideration. Despite these limitations, the adverse prognosis of patients with COVID-19 and CI has been consistently demonstrated.
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Cyclin-dependent kinase (CDK) 4/6 inhibitors have emerged in the treatment of metastatic hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, most patients will eventually present disease progression, highlighting the inevitable resistance of cancer cells to CDK4/6 inhibition. Several studies have suggested that resistance mechanisms involve aberrations of the molecules that regulate the cell cycle, and the re-wiring of the cell to escape CDK4/6 dependence and turn to alternative pathways. Loss of retinoblastoma function, overexpression of CDK 6, upregulation of cyclin E, overexpression of CDK 7, and dysregulation of several signaling pathways, notably the PI3/AKT/mTOR pathway, have been implicated in the development of resistance to CDK4/6 inhibitors. Overlap with endocrine resistance mechanisms might be possible. Combinational therapeutic strategies should be explored in order to prevent resistance and optimize the management of patients after progression under CDK 4/6 inhibition.
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Neoplasias da Mama/genética , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Ciclina E/genética , Ciclina E/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Terapia de Alvo Molecular/métodos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Quinase Ativadora de Quinase Dependente de CiclinaRESUMO
BACKGROUND: Chlamydia pneumoniae is a common cause of atypical community acquired pneumonia (CAP). The diagnostic approach of chlamydial infections remains a challenge. Diagnosis of delayed chlamydial-associated complications, involving complex autoimmune pathophysiological mechanisms, is still more challenging. C. pneumoniae-related cardiac complications have been rarely reported, including cases of endocarditis, myocarditis and pericarditis. CASE PRESENTATION: A 40-year old female was hospitalized for pleuropericarditis following lower respiratory tract infection. The patient had been hospitalized for CAP (fever, dyspnea, chest X-ray positive for consolidation on the left upper lobe) 5 weeks ago and had received ceftriaxone and moxifloxacin. Four weeks after her discharge, the patient presented with fever, shortness of breath and pleuritic chest pain and was readmitted because of pericardial and bilateral pleural effusions (mainly left). The patient did not improve on antibiotics and sequential introduction of colchicine and methylprednisolone was performed. The patient presented impressive clinical and laboratory response. Several laboratory and clinical assessments failed to demonstrate any etiological factor for serositis. Chlamydial IgM and IgG antibodies were positive and serial measurements showed increasing kinetics for IgG. Gold standard polymerase chain reaction of respiratory tract samples was not feasible but possibly would not have provided any additional information since CAP occurred 5 weeks ago. The patient was discharged under colchicine and tapered methylprednisolone course. During regular clinic visits, she remained in good clinical condition without pericardial and pleural effusions relapse. CONCLUSIONS: C. pneumoniae should be considered as possible pathogen in case of pleuritis and/or pericarditis during or after a lower respiratory tract infection. In a systematic review of the literature only five cases of C. pneumoniae associated pericarditis were identified. Exact mechanisms of cardiovascular damage have not yet been defined, yet autoimmune pathways might be implicated.
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Infecções por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/isolamento & purificação , Pericardite/microbiologia , Adulto , Infecções por Chlamydophila/complicações , Feminino , Humanos , Pericardite/diagnósticoRESUMO
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has long been implicated in modeling antitumor immunity; PD-1/PD-L1 axis inhibitors exert their antitumor effects by relieving PD-L1-mediated suppression on tumor-infiltrating T lymphocytes. However, recent studies have unveiled a distinct, tumor-intrinsic, potential role for PD-L1. In this review, we focus on tumor-intrinsic PD-L1 signaling and delve into preclinical evidence linking PD-L1 protein expression with features of epithelial-to-mesenchymal transition program, cancer stemness and known oncogenic pathways. We further summarize data from studies supporting the prognostic significance of PD-L1 in different tumor types. We show that PD-L1 may indeed have oncogenic potential and act as a regulator of tumor progression and metastasis.
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Antígeno B7-H1/metabolismo , Metástase Neoplásica/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Progressão da Doença , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Prognóstico , Transdução de Sinais/fisiologiaRESUMO
Tumor dormancy refers to a critical stage of cancer development when tumor cells are present, but cancer does not progress. It includes both the concept of cellular dormancy, indicating the reversible switch of a cancer cell to a quiescent state, and that of tumor mass dormancy, indicating the presence of neoplastic masses that have reached cell population equilibrium via balanced growth/apoptosis rates. Tumor dormancy provides the conceptual framework, potentially explaining a major challenge in clinical oncology, tumor recurrence, which may occur years after cancer diagnosis. The mechanisms by which tumors are kept dormant, and what triggers their reawakening, are fundamental questions in cancer biology. It seems that a plethora of intracellular pathways and extracellular factors are involved in this process, rewiring the cells to plastically alter their metabolic and proliferative status. This phenomenon is highly dynamic in space and time. Mechanistic insights into both cellular and tumor dormancy have provided the rationale for targeting this otherwise stable period of cancer development, in order to prevent recurrence and maximize therapeutic benefit.
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MicroRNAs/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Animais , Apoptose/genética , Autofagia/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Microambiente Tumoral/genéticaRESUMO
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable.
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Worldwide, approximately half of the patients diagnosed with lung cancer (LC) will develop, simultaneously or asynchronously, brain metastases (BMs). The existence of BMs negatively affects the quality of life and constitutes a poor prognostic factor, linked with high mortality. Locoregional therapy with surgery or radiation is, until now, the treatment of choice, especially for symptomatic patients; however, both options are linked to a high complication rate. The question arising here is whether, in asymptomatic patients, the benefit outweighs the risk and whether an alternative method can be used to treat this special category of patients. Over the last decade, immune checkpoint inhibitors (ICIs) have represented a major breakthrough in the field of oncology, and several molecules have been approved as a treatment option for LC. This review tried to analyze the tumor microenvironment of both the primary lung tumor and the BMs in order to evaluate the intracranial activity of ICIs, outline the main challenges of including these agents in the treatment of LC with BMs, highlight the available information from the main clinical trials, and mark the potential positive effect of choosing a combination therapy. In conclusion, it appears that immunotherapy has a positive effect, inhibiting the progression of BMs, but more data should be published specifically for this category of patients.
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Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. The distinction between RWD and data derived from randomized clinical trials lies in the method of data collection, as RWD by definition are obtained at the point of care. Experimental designs resembling those used in traditional clinical trials can be utilized to generate RWD, thus offering multiple benefits including increased efficiency and a more equitable balance between internal and external validity. Real-world data can be utilized in the field of pharmacovigilance to facilitate the understanding of disease progression and to formulate external control groups. By utilizing prospectively collected RWD, it is feasible to conduct pragmatic clinical trials (PCTs) that can provide evidence to support randomized study designs and extend clinical research to the patient's point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly and patients with poor performance status (PS), hepatitis, or human immunodeficiency virus, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.
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BACKGROUND: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. METHODS: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested. RESULTS: In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively). CONCLUSION: Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE.
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The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib.
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The aim of the present review was to extend research by reviewing international research regarding the communication between oncologists and oncology patients and the communication of bad news to oncology patients during the COVID-19 pandemic. Following the PRISMA guidelines a review of the literature was performed by searching PubMed, Scopus, and EMBASE bibliographic databases from inception to October 10, 2022. The search was limited to articles written in English. Two reviewers independently completed title and abstract, full-text screening, and data extraction. A total of five studies were deemed eligible for this systematic review. A narrative synthesis was undertaken. Of these five articles, three referred to the communication of bad news to patients by medical oncologists during the COVID-19 pandemic, whereas the remaining two referred to the transmission of bad news to patients by surgeons during the pandemic. The COVID-19 pandemic and the social distancing measures imposed caused radical changes in the forms of communication in medical environments. The challenges faced by the oncologist in breaking bad news to cancer patients are highlighted in this systematic review, and the need for physician preparation prior to communication with the patient is emphasized. Overall, new studies are needed on the effects of distance communication on both health professionals and patients. New studies are also needed that would explore the perceptions of physicians and patients in Greece.
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COVID-19 , Neoplasias , Humanos , Relações Médico-Paciente , Revelação da Verdade , Pandemias , COVID-19/epidemiologia , Neoplasias/epidemiologia , Neoplasias/diagnóstico , ComunicaçãoRESUMO
Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies arising from the thymus gland. The optimal management requires a multidisciplinary approach. Standard first-line systemic treatment involves cytotoxic chemotherapeutic regimens; however, alternative options for systemic treatment are required. Current research focuses on the unique profile of immune-related pathogenic mechanisms of TETs, involving an overlap with certain autoimmune phenotypes, as well as on determining the landscape of oncogenic molecular alterations and the role of tumor angiogenesis. The aim of the present review is to summarize the current clinical investigation on immunotherapy and targeted agents in the management of TETs. Regarding immune checkpoint inhibitors, efficacy results are promising in certain subsets of patients; however, caution is required concerning their toxicity. Anti-angiogenic agents, mainly potent small-molecule inhibitors, have demonstrated antitumor activity in TETs, whereas other targeted agents, including KIT inhibitors and epigenetic agents, are associated with encouraging, yet still modest results for unselected populations, in the absence of predictive biomarkers. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types.
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BACKGROUND/AIM: Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece. PATIENTS AND METHODS: From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed. Exploratory end-points included the incidence of intubation, probability of recovery, mortality, and duration of remdesivir (RDV) administration. RESULTS: Overall, mechanical ventilation (MV) was required for five patients and crude mortality was 8.3%. HM of lymphocytic origin (p=0.035) and obesity (p=0.03) were the main determinants of the risk of intubation and among several laboratory markers, only LDH>520 IU/l was proven to be an independent MV predictor (p=0.038). The number of co-existing comorbidities (p=0.05) and disease severity on admission (p<0.001) were found to rule the probability of recovery, and dexamethasone was associated with worse prognosis, particularly in patients with mild/moderate COVID-19. RDV was administered to the entire cohort, of whom 38 were managed with an extended course. In the multivariate analysis, patients with HM of lymphocytic origin were more likely to receive RDV for more than five days (p=0.002). CONCLUSION: Our study emphasizes the frailty of HM patients, even in the era of Omicron-variant predominance, and underlines the need to optimize therapy.
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COVID-19 , Neoplasias Hematológicas , Humanos , Adulto , SARS-CoV-2 , COVID-19/epidemiologia , Estudos Retrospectivos , Neoplasias Hematológicas/complicações , VacinaçãoRESUMO
INTRODUCTION: NELSON and NLST prompted the implementation of lung cancer screening programs in the United States followed by several European countries. This study aimed to assess the sensitivity of different screening criteria among patients with lung cancer in Greece and investigate reasons for ineligibility. METHODS: We performed a retrospective analysis on patients with lung cancer referred to the largest referral center in Athens, Greece, between June 2014 and May 2023. The proportion of patients who would meet the updated USPSTF and NLST criteria was compared to the corresponding proportion of the Greek population over 15 years of age. RESULTS: Out of 2434 patients with lung cancer, 77.4 % (N = 1883) would meet the updated USPSTF criteria, and 58.9 % (N = 1439) would meet the NLST criteria at diagnosis; the corresponding proportions for the Greek population over 15 years would be 13.8 % and 8.2 %, respectively. Ineligible patients were more likely to be female, former or never-smokers, have adenocarcinoma histology, and have driver mutations (p < 0.001). CONCLUSIONS: Although the updated USPSTF criteria demonstrated good sensitivity, a substantial proportion of patients with lung cancer would still not be eligible for screening. Future studies to shape a comprehensive screening strategy should focus on the incorporation of additional risk factors for lung cancer, including air pollution and individual genetic susceptibility.
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Neoplasias Pulmonares , Humanos , Feminino , Estados Unidos , Masculino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Grécia/epidemiologia , Estudos Retrospectivos , Detecção Precoce de Câncer , Fumar/efeitos adversos , Programas de Rastreamento , Tomografia Computadorizada por Raios XRESUMO
The introduction of immune checkpoint inhibitors in the therapeutics of non-small cell lung cancer (NSCLC) has been a game-changer in the management of patients with lung cancer; however, challenges do exist since a non-negligible subset of patients does not respond to therapy. Various immunotherapeutic anticancer strategies have been increasingly developed in recent years, including monoclonal antibodies, adoptive T-cell therapy, and vaccines. Fueled by their rapid drug development and successful implementation during the COVID-19 pandemic, messenger RNA (mRNA) vaccines represent an emerging therapeutic approach in other fields of medicine, including oncology. Several clinical trials are currently being conducted to assess the safety and efficacy of mRNA vaccines regarding a variety of solid tumors. Combining mRNA vaccines with other immunotherapeutic approaches has also been suggested and is currently under investigation. Although, in the case of NSCLC, the investigation is still in its early stages, the initial results raise the need for clinician awareness of these promising therapies. To this end, in the present review, we aim to summarize current advances in the development of mRNA vaccines in NSCLC therapeutics and discuss pragmatic challenges regarding their drug development and the different opportunities for implementation.
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Capecitabine is an oral 5-fluorouracil prodrug with antimetabolite activity commonly used in advanced colorectal and breast cancer. It presents with a generally good toxicity profile and most of the adverse events can be managed effectively. Enterocolitis is a rare, under-reported, but potentially fatal adverse event associated with capecitabine use. To the best of our knowledge, there are 21 cases of capecitabine-related enterocolitis reported in the literature. We herein present a narrative literature review of enteritis/colitis cases associated with capecitabine use, with highlight to the most common clinical presentation, common imaging and microscopic findings and management approach. We furthermore present a case of severe capecitabine-related enteritis.
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Enterite , Enterocolite , Humanos , Capecitabina/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina , Fluoruracila/efeitos adversos , Enterocolite/induzido quimicamente , Enterite/induzido quimicamenteRESUMO
Malignancies are among the leading causes of mortality worldwide. Early detection and treatment are the primary targets of clinical and translational research, and may be facilitated by the recognition of novel diagnostic and prognostic biomarkers. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily of proteins (TNFRSF), which associates with its respective TNF-like ligands, Fas-L, LIGHT, and TL1A. DcR3 has been recognised as a significant anti-apoptotic factor with prominent involvement in various inflammatory and neoplastic conditions. Increased intratumor expression of DcR3 and elevated soluble DcR3 protein content in the sera of patients has been reported for various malignancies. Recent published work has suggested that monitoring of local and systemic DcR3 may provide an attractive biomarker, mainly for defining subgroups of patients with aggressive tumor behaviour and poor prognosis. The aim of the present review is to summarize and critically present existing evidence regarding the potential clinical importance of monitoring DcR3 expression in patients with malignancies of the gastrointestinal tract, as well as liver and pancreatic cancer. We also present a detailed description of the pathophysiological basis that may underlie the involvement of DcR3 in gastrointestinal carcinogenesis. Based on these data, we comment on the potential applicability of DcR3 monitoring in the diagnosis and, most importantly, the prognostic stratification of patients.
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Since the pandemic's onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. So far, several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms. Excessive cytokine release, impaired T-cell responses, aberrant activation of regulatory signaling pathways (e.g., JAK-STAT, MAPK, NF-kB), and tissue damage, hallmarks of COVID-19 disease course, are also present in the tumor microenvironment. Therefore, the intersection of COVID-19 and cancer is partially recognized and the long-term effects of the virus on oncogenesis and cancer progression have not been explored yet. Herein, we present an up-to-date review of the current literature regarding COVID-19 and cancer cross-talk, as well as the oncogenic pathways stimulated by SARS-CoV-2.