mRNA expression, tumor heterogeneity, and response to therapy in patients with advanced renal cell carcinoma treated with immune-based combinations (ARON-1α).

Background: Renal Cell Carcinoma (RCC) represents a spectrum of tumors, characterized by heterogeneous growth patterns, histology and response to immune-based combinations.

Objectives: The aim of the present retrospective analysis was to investigate the mRNA expression of 32 genes associated with RCC carcinogenesis and their potential involvement in patients treated with first-line immune-based combination therapies. Additionally, we examined the role of tumor heterogeneity by comparing mRNA expression levels between primary renal tumors and metastatic sites in a group of patients included in the ARON-1 study.

Baseline metabolic signatures predict clinical outcomes in immunotherapy-treated melanoma patients: a pilot study.

Background: Immune checkpoint inhibitors (ICIs) have improved the metastatic melanoma (MM) treatment. However, a significant proportion of patients show resistance to immunotherapy, and predictive biomarkers for non-responders or high-risk recurring patients are currently lacking. Recent studies have shown that tumor-related metabolic fingerprints can be useful in predicting prognosis and response to therapy in various cancer types.

BRCA cascade counselling and testing in Italy: current position and future directions.

Background: Genetic testing has led to a considerable enhancement in the ability to identify individuals at risk of Hereditary Breast and Ovarian Cancer syndrome related to BRCA1/2 pathogenic variants, thus necessitating personalised prevention programs. However, barriers related to intrafamilial communication, privacy regulations, and genetic information dissemination hinder preventive care, particularly in Italy, where legal constraints limit the disclosure of genetic risks to at-risk relatives. This study examines the relationship between BRCA1/2 carriers' communication challenges and three factors: cancer status, comprehension of genetic information, and the genetic counseling pathway accessed (Traditional Genetic Counseling, TGC vs.

Liquid Biopsy: The Challenges of a Revolutionary Approach in Oncology.

Liquid biopsy has gained attention in oncology as a non-invasive diagnostic tool, offering valuable insights into tumor biology through the analysis of circulating nucleic acid (cfDNA and cfRNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and tumor-educated platelets (TEPs). In this review, we summarize the clinical use of liquid biopsies in cancer now and look forward to its future, with a particular emphasis on some the methods used to isolate the liquid biopsy analytes. This technique provides real-time information on tumor dynamics, treatment response, and disease progression, with the potential for early diagnosis and personalized treatment.

Insight into the Regulation of NDRG1 Expression.

The N-Myc Downstream Regulated Gene 1 (NDRG1) protein, a member of a family of four, has emerged as a key regulator of various physiological and pathological processes. Extensive knowledge has been gained on the modulation of NDRG1 expression during endoplasmic reticulum stress, autophagy, and hypoxia. Moreover, new functions have emerged in recent years.

Screening for psychological distress in cancer care: prevalence and predictive factors among Italian patients using the Concerns and Help Identifier for Medical Patients Checklist.

Purpose: Psychological distress is highly prevalent among cancer patients. Although several scientific and professional organizations developed guidelines and tools for screening, implementation barriers in cancer care persist. Therefore, it seems to be critical to effectively introduce tools and triage systems that can identify patients' source of distress.

Liquid biopsy for guiding breast cancer immunotherapy.

Liquid biopsy is a laboratory test used to detect and analyze circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and other tumor-derived components, in a blood sample. In the context of breast cancer (BC), liquid biopsies hold significant promise for guiding the use of immune checkpoint inhibitors and immune-based combinations, offering real-time insights into tumor dynamics, treatment response, and resistance mechanisms. This review explores the role of liquid biopsy in BC immunotherapy, focusing on its applications, benefits, issues, and current and future research directions.

Developing a risk score using liquid biopsy biomarkers for selecting Immunotherapy responders and stratifying disease progression risk in metastatic melanoma patients.

Background: Despite the high response rate to PD-1 blockade therapy in metastatic melanoma (MM) patients, a significant proportion of patients do not respond. Identifying biomarkers to predict patient response is crucial, ideally through non-invasive methods such as liquid biopsy.

Methods: Soluble forms of PD1, PD-L1, LAG-3, CTLA-4, CD4, CD73, and CD74 were quantified using ELISA assay in plasma of a cohort of 110 MM patients, at baseline, to investigate possible correlations with clinical outcomes.

Immunobiology of biliary tract cancer and recent clinical findings in approved and upcoming immune checkpoint inhibitors.

Introduction: Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches.

Areas Covered: In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials.

Corrigendum: The molecular tumor board as a step in cancer patient management: a southern Italian experience.

[This corrects the article DOI: 10.3389/fmed.2024.

The molecular tumor board as a step in cancer patient management: a southern Italian experience.

Introduction: The management of cancer patients follows a Diagnostic Therapeutic and Care Pathway (PDTA) approach, aimed at achieving the optimal balance between care and quality of life. To support this process, precision medicine and innovative technologies [e.g.

Case report: Germline mutation in a patient with GIST and lung adenocarcinoma.

The gene () is involved in telomere maintenance and stability and plays a crucial role in the preservation of genomic stability. is considered a high-penetrance melanoma susceptibility gene; however, the number of cancer types associated with the pathogenic germline variants of is gradually increasing, including chronic lymphocytic leukemia (CLL), angiosarcomas, and gliomas, even though many associations are still elusive. Here, we reported a case of a 60-year-old man who showed early-onset multiple neoplasms, including multiple melanomas, gastrointestinal stromal tumor (GIST), and lung adenocarcinoma.

The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials.

Background: We performed a systematic review and meta-analysis to further explore the impact of the addition of immunotherapy to gemcitabine-cisplatin as first-line treatment for advanced biliary tract cancer (BTC) patients.

Methods: Literature research was performed, and hazard ratio values and 95% confidence intervals were calculated. Heterogeneity among studies was assessed using the tau-squared estimator .

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses.

Benchmarking and improving the performance of variant-calling pipelines with RecallME.

Motivation: The steady increment of Whole Genome/Exome sequencing and the development of novel Next Generation Sequencing-based gene panels requires continuous testing and validation of variant calling (VC) pipelines and the detection of sequencing-related issues to be maintained up-to-date and feasible for the clinical settings. State of the art tools are reliable when used to compute standard performance metrics. However, the need for an automated software to discriminate between bioinformatic and sequencing issues and to optimize VC parameters remains unmet.

Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma.

Background: Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI.

Tumor Cellularity Assessment of Breast Histopathological Slides via Instance Segmentation and Pathomic Features Explainability.

The segmentation and classification of cell nuclei are pivotal steps in the pipelines for the analysis of bioimages. Deep learning (DL) approaches are leading the digital pathology field in the context of nuclei detection and classification. Nevertheless, the features that are exploited by DL models to make their predictions are difficult to interpret, hindering the deployment of such methods in clinical practice.

The role of unpaired image-to-image translation for stain color normalization in colorectal cancer histology classification.

Background: Histological assessment of colorectal cancer (CRC) tissue is a crucial and demanding task for pathologists. Unfortunately, manual annotation by trained specialists is a burdensome operation, which suffers from problems like intra- and inter-pathologist variability. Computational models are revolutionizing the Digital Pathology field, offering reliable and fast approaches for challenges like tissue segmentation and classification.

Communications Is Time for Care: An Italian Monocentric Survey on Human Papillomavirus (HPV) Risk Information as Part of Cervical Cancer Screening.

Human papilloma virus (HPV) infection could be considered a social disease, both for its high incidence, especially in younger subjects, and for the risk of neoplastic evolution linked to viral infection. Therefore, the National Health System, in collaboration with the state, must help women to understand the oncological risk of HPV and suitable methods of prevention. We conducted an Italian monocentric survey on HPV risk information as part of cervical cancer screening.

NDG-CAM: Nuclei Detection in Histopathology Images with Semantic Segmentation Networks and Grad-CAM.

Nuclei identification is a fundamental task in many areas of biomedical image analysis related to computational pathology applications. Nowadays, deep learning is the primary approach by which to segment the nuclei, but accuracy is closely linked to the amount of histological ground truth data for training. In addition, it is known that most of the hematoxylin and eosin (H&E)-stained microscopy nuclei images contain complex and irregular visual characteristics.

Remote vs in-person BRCA1/2 non-carriers test disclosure: patients' choice during Covid-19 pandemic restriction.

During Covid-19 pandemic most hospitals have restricted in-person delivery of non-essential healthcare services, including genetic testing delivery, to slow the spread of the virus. Our Onco-Genetic Service also faced this challenging period and had to re-organize its clinical practice with the use of tele-health. Aim of the present paper is to understand whether and how Covid-19-related changes in medical practice influenced patients' satisfaction about the health service provided.

NR1H3 (LXRα) is associated with pro-inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b-cell lymphoma.

The role of macrophages (Mo) and their prognostic impact in diffuse large B-cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver-X-Receptors (LXRs) control Mo polarization/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes.

Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report.

Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients.

Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma.

Background: The immunotherapy with immune checkpoints inhibitors (ICI) has changed the life expectancy in metastatic melanoma (MM) patients. Nevertheless, several patients do not respond hence, the identification and validation of novel biomarkers of response to ICI is of crucial importance. Circulating extracellular vesicles (EVs) such as PD-L1 EV mediate resistance to anti-PD1, instead the role of PD1 EV is not fully understood.