Inflammation-related biomarkers as predictors of pathological complete response in early-stage breast cancer.

Background: Neoadjuvant systemic therapy (NAT) represents an attractive option for improved outcomes of early-stage breast cancer (BC) patients, as it can significantly reduce tumor burden thus permitting breast-conserving resections. Equally important, the eradication of viable cancer cells post-NAT, also known as pathological complete response (pCR), has emerged as a strong prognostic biomarker, reflecting tumor's biology and subsequent treatment responses. Yet to date, no validated markers predictive of pCR have been identified.

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies.

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10-15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST).

Mechanisms of primary resistance to immune checkpoint inhibitors in NSCLC.

Immune checkpoint inhibitors (ICIs) redefined the therapeutics of non-small cell lung cancer (NSCLC), leading to significant survival benefits and unprecedented durable responses. However, the majority of the patients develop resistance to ICIs, either primary or acquired. Establishing a definition of primary resistance to ICIs in different clinical scenarios is challenging and remains a work in progress due to the changing landscape of ICI-based regimens, mainly in the setting of early-stage NSCLC.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study.

Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC.

Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone.

CAR-T Cell Therapy in Pancreatic and Biliary Tract Cancers: An Updated Review of Clinical Trials.

Background: Pancreatic and biliary tract cancers are digestive system tumors with dismal prognosis and limited treatment options. The effectiveness of conventional surgical interventions, radiation therapy, and systemic therapy is restricted in these cases. Furthermore, clinical trials have shown that immunotherapy using immune checkpoint inhibitors has only demonstrated modest clinical results when applied to patients with pancreatobiliary tumors.

A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion.

Progress and Challenges of Messenger RNA Vaccines in the Therapeutics of NSCLC.

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.

Molecular interactions of antibodies with PD-1/PD-L1 proteins.

To compare the protein-protein interactions of antibodies targeting PD-1 and its ligand (PD-L1) with their targets in an attempt to explain the antibodies' binding affinity. The structural features of complexes between pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab and PD-1/PD-L1 are described, with the use of software and based on crystallographic data. Pembrolizumab has more structural features, including the number and type of the bonds and total binding surface area, which could rationalize its different clinical behavior compared with nivolumab.

Estrogen-Receptor-Low-Positive Breast Cancer: Pathological and Clinical Perspectives.

The expression of estrogen receptors (ERs) in breast cancer (BC) represents a strong prognostic and predictive biomarker and directs therapeutic decisions in early and advanced stages. ER-low-positive BC, defined by the immunohistochemical (IHC) expression of ERs from 1% to 9%, constitutes a distinct subset of total BC cases. Guidelines recommend that a low expression of ERs be reported in pathology reports since the benefit of endocrine therapy in patients with ER-low-positive BC is uncertain.

An overview of the role of telomeres and telomerase in pre‑neoplastic lesions (Review).

Telomeres are tandem repeats of DNA sequences protecting the end of linear chromosomes. Replicative senescence due to telomere attrition is considered a tumor-preventing mechanism in differentiated somatic cells. However, telomere shortening is associated with genome instability and several disease entities.

The Role of REV-ERB Receptors in Cancer Pathogenesis.

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.

Lung microbiome: an emerging player in lung cancer pathogenesis and progression.

The microbiome of the lungs, although until recently neglected, is now emerging as a potential contributor to chronic lung diseases, including cancer. Preclinical evidence suggests that the microbial burden of the lungs shapes the host immunity mechanisms and affects local antitumor immune responses. Studies of cohorts of patients with lung cancer reveal that different microbiome profiles are detected in patients with lung cancer compared to controls.

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options.

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.

Emerging therapies in thymic epithelial tumors (Review).

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.

Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives.

Anti-programmed cell death protein 1 immunotherapy has been incorporated in the treatment algorithm of triple-negative breast cancer (TNBC). However, clinical trial results for patients with hormone receptor (HR)-positive disease appear less compelling. HR-positive tumors exhibit lower levels of programmed death-ligand 1 expression in comparison with their triple-negative counterparts.

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment.

BRAF/MEK inhibition in NSCLC: mechanisms of resistance and how to overcome it.

Targeted therapy for oncogenic genetic alterations has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). Mutations in the BRAF gene are detected in approximately 4% of patients and result in hyper-activation of the MAPK pathway, leading to uncontrolled cellular proliferation. Inhibition of BRAF and its downstream effector MEK constitutes a therapeutic strategy for a subset of patients with NSCLC and is associated with clinical benefit.

Assessment of Seroconversion after SARS-CoV-2 Vaccination in Patients with Lung Cancer.

Background: SARS-CoV-2 mortality rates are significantly higher in patients with lung cancer compared with the general population. However, little is known on their immunization status after vaccination. Methods: To evaluate the humoral response (seroconversion) of patients with lung cancer following vaccination against SARS-COV-2 (Group A), we obtained antibodies against SARS-CoV-2 spike (S) protein both at baseline and at different time points after the first dose of SARS-CoV-2 vaccine (two to three weeks [T1], six weeks ± one week [T2], 12 weeks ± three weeks [T3], and 24 weeks ± three weeks [T4]).

Capecitabine-associated enterocolitis: Narrative literature review of a rare adverse event and a case presentation.

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.

Pulmonary blastoma: a comprehensive overview of a rare entity.

Introduction: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component.

Programmed Death-Ligand 1 as a Regulator of Tumor Progression and Metastasis.

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.

Tumor Dormancy: Implications for Invasion and Metastasis.

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.

Risk Factors for Venous Thromboembolism in Patients With Small Cell Lung Cancer.

Background/aim: Small cell lung cancer (SCLC) accounts for 13% of all lung cancers. Venous thromboembolism (VTE) is a frequent complication. The purpose of this study was to investigate the incidence and risk factors for VTE in SCLC patients.

The changing treatment of metastatic her2-positive breast cancer.

Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been historically associated with an aggressive disease course with common distant metastasis and poor prognosis. HER2-targeting therapies have significantly changed treatment and drastically improved outcomes for this group of patients. However, primary or acquired resistance to anti-HER2 regimens leads almost universally to disease progression, often with difficult to treat central nervous system (CNS) metastases.

Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors.

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.