Combined Therapeutic Strategies Based on the Inhibition of Non-Oncogene Addiction to Improve Tumor Response in EGFR- and KRAS-Mutant Non-Small-Cell Lung Cancer.

Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting drugs in the first and second line, respectively. Unfortunately, the development of oncogene-independent resistant clones limits TKI efficacy.

Functional effect of adiponectin and body composition assessment in lung cancer subjects after video-assisted thoracoscopic surgery (VATS) lobectomy.

Background: Lung cancer is a pathology with an important incidence. It is a multifactorial disease characterized by epigenetic and nutritional factors. Indeed, there is a strong association between adipose tissue and the pulmonary system, and low-grade inflammation of obese and/or overweight subjects have a pivotal role in lung cancer establishment.

Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [F]FDG Alternatives.

Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation.

Discovery of -substituted-2-oxoindolin benzoylhydrazines as c-MET/SMO modulators in EGFRi-resistant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), the leading cause of cancer-related mortality worldwide, poses a formidable challenge due to its heterogeneity and the emergence of resistance to targeted therapies. While initially effective, first- and third-generation EGFR-tyrosine kinase inhibitors (TKIs) often fail to control disease progression, leaving patients with limited treatment options. To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC.

Unleashing precision: A review of targeted approaches in pleural mesothelioma.

This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers.

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.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease.

Post-Irradiation Breast Angiosarcoma: All the Possible Treatments and Electrochemotherapy. Case Report and Literature Review.

Breast angiosarcoma is a rare malignancy, accounting for less than 1% of all soft tissue cancers. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite multimodal treatment, angiosarcomas represent an incurable disease for many patients and a significant cause of deterioration in their quality of life.

ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors.

Background: ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which provides metabolic intermediates to sustain cell proliferation. The aim of our study is to elucidate the role of ATM in the regulation of glucose metabolism in oncogene-driven cancer cells and to test whether ATM may be a suitable target for anticancer therapy.

Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial.

The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B).

CARdioimaging in Lung Cancer PatiEnts Undergoing Radical RadioTherapy: CARE-RT Trial.

Background: Non-small-cell lung cancer (NSCLC) is a common, steady growing lung tumour that is often discovered when a surgical approach is forbidden. For locally advanced inoperable NSCLC, the clinical approach consists of a combination of chemotherapy and radiotherapy, eventually followed by adjuvant immunotherapy, a treatment that is useful but may cause several mild and severe adverse effect. Chest radiotherapy, specifically, may affect the heart and coronary artery, impairing heart function and causing pathologic changes in myocardial tissues.

Panitumumab Plus Trifluridine-Tipiracil as Anti-Epidermal Growth Factor Receptor Rechallenge Therapy for Refractory RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Current third-line therapies for patients with metastatic colorectal cancer (MCRC) have limited efficacy. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors for RAS wild-type (WT) MCRC may be valuable for these patients.

Objective: To compare the anti-EGFR monoclonal antibody panitumumab plus standard-of-care trifluridine-tipiracil with trifluridine-tipiracil alone as third-line therapy for RAS WT MCRC.

A Critical Issue in Lung Cancer Cytology and Small Biopsies: DNA and RNA Extraction from Archival Stained Slides for Biomarker Detection through Real Time PCR and NGS-The Experience in Pathological Anatomy Unit.

The handling of biomaterials is crucial for precision medicine in advanced-stage lung patients with only cytology or small biopsies available. The main purpose of the study was to evaluate the quantity and quality of nucleic acids extracted from mixed stained slides (MSSs), including H&E, IHC and FISH, compared to the extraction from unstained slides (USs). A series of 35 lung adenocarcinoma surgical samples was selected to set up the method and the technical approach was validated in a series of 15 small biopsies and 38 cytological samples.

PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype.

Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED).

Antitumor Efficacy of Dual Blockade with Encorafenib + Cetuximab in Combination with Chemotherapy in Human BRAFV600E-Mutant Colorectal Cancer.

Purpose: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC.

Experimental Design: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts.

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer.

Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD).

The prognostic value of histopathology in invasive lung adenocarcinoma: a comparative review of the main proposed grading systems.

Introduction: An accurate histological evaluation of invasive lung adenocarcinoma is essential for a correct clinical and pathological definition of the tumour. Different grading systems have been proposed to predict the prognosis of invasive lung adenocarcinoma.

Areas Covered: Invasive non mucinous lung adenocarcinoma is often morphologically heterogeneous, consisting of complex combinations of architectural patterns with different proportions.

Role of Cardiac Biomarkers in Non-Small Cell Lung Cancer Patients.

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score).

AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors.