Early-onset colorectal cancer patients exhibit a distinct molecular fingerprint: insights from a large-scale NGS study of 1209 patients.

Background: Early-onset colorectal cancer (EO-CRC, ≤50 years of age) exhibits unique clinical and biological characteristics when compared with average-onset CRC (AO-CRC), but its overall molecular profile is still not well studied.

Materials And Methods: We retrospectively analysed 1209 patients with metastatic CRC profiled using FoundationOne® CDx, a clinically validated next-generation sequencing assay targeting 324 cancer-related genes. Patients were classified as EO-CRC (n = 298) or AO-CRC (n = 911).

Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions.

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC.

The impact of the fetal exposome as a predictor of cancer risk in childhood and adulthood. Aberrant epigenetic events occurring during gestation: May they trigger fetal programming of cancer risk later in life?

The rising incidence of cancer, particularly among children and young adults, has led to renewed interest in the early-life origins of the disease. The fetal programming hypothesis, originally proposed by Barker, posits that environmental disruptions during intrauterine development can induce long-lasting molecular and structural changes that increase susceptibility to diseases, including cancer, later in life. This narrative review examines how prenatal exposures, such as maternal malnutrition, alcohol use, exposure to toxins, obesity, and hormonal imbalances, may epigenetically reprogram the developing fetus, influencing cancer risk throughout the lifespan.

Cancer-associated fibroblasts (CAFs) and plaque-associated fibroblasts (PAFs): Unraveling the cellular crossroads of atherosclerosis and cancer.

Atherosclerosis is a complex process involving various cells and molecules within the atherosclerotic plaque. Recent evidence suggests that plaque-associated fibroblasts (PAFs), also known as atherosclerosis-associated fibroblasts (AAFs), might play a significant role in the development and progression of the disease. The microenvironment of the atherosclerotic plaque, resembling the tumor microenvironment (TME), includes various cellular populations like plaque-associated macrophages (PAMs), plaque-associated neutrophils (PANs), vascular smooth muscle cells (VSMCs), myeloid-derived suppressor cells (MDSCs), and PAFs.

Liquid biopsy: An innovative tool in oncology. Where do we stand?

The Liquid Biopsy (LB) represents an ideal surrogate of tumor Tissue Biopsy (TB) when the aim is to obtain useful information on patient prognosis and personalized therapy. This technique renders it possible to isolate circulating tumor cells, circulating tumor DNA and other molecules from biological fluids. The most commonly used fluid for liquid biopsy is blood, but depending on the case it could be necessary to isolate the tumor components from other biological fluids such as urine, pleural effusion, cerebrospinal fluid, and others.

Preoperatory FLOT Regimen for Gastroesophageal Cancer and Renal Function: A New Onco-Nephrological Perspective.

Background: The FLOT regimen, a combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel, is a standard treatment for gastric and esophagogastric junction cancers, but concerns exist about its potential renal toxicity. The exact prevalence and severity of renal toxicity need to be well documented, and this knowledge gap could impact the optimal use of the FLOT regimen in clinical practice. We aimed to evaluate the renal toxicity profile of the FLOT regimen with a specific focus on acute kidney disease (AKD) onset in a real-life setting and explore associated risk factors.

The evolving landscape of stage III unresectable non-small cell lung cancer "between lights and shadows".

Despite PACIFIC set a new milestone in the clinical management of unresectable stage III non-small cell lung cancer (NSCLC), it left some critical questions pending for clinical research: the efficacy of durvalumab in the real-world setting; the activity of less intensive regimens for frail populations; the role of targeted therapies in oncogene-addicted tumors; the selection of subsequent strategies at immunotherapy failure; the efficacy of novel and intensified treatments; the role of molecular biomarkers for patients' selection. This review aims to describe the evolving landscape of unresectable stage III NSCLC and provides an updated overview of the available evidence, analyzing lights and shadows emerging from recent clinical trials and discussing the most relevant challenges of post-PACIFIC era.

Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy.

Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.

Objectives: We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.

An evaluation of talazoparib plus enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

Introduction: Prostate cancer (PCa) is the second most common cancer diagnosis among men worldwide, with poor prognosis in its advanced stage. Treatment strategies have evolved, including the use of androgen receptor pathway inhibitors (ARPIs) and poly (ADP-ribose) polymerase inhibitors (PARPis).

Areas Covered: This review evaluates the clinical efficacy, safety, and future potential of combining talazoparib, a potent PARPi, with enzalutamide, a strong androgen receptor (AR) antagonist.

Early onset metastatic colorectal cancer patients as a distinctive clinical and molecular phenomenon.

Background: Despite a reduction of both incidence and mortality from CRC, recent studies have shown an increase in the incidence of early-onset CRC (EO-CRC). Data on this setting are limited. The aim of our study was to evaluate the clinical and molecular profiles of metastatic EO-CRC patients in order to identify differences compared to a late-onset CRC (LO-CRC) control group.

Role of osimertinib plus brain radiotherapy versus osimertinib single therapy in EGFR-mutated non-small-cell lung cancer with brain metastases: A meta-analysis and systematic review.

Single-agent osimertinib has improved outcomes in EGFR-mutated lung cancer patients with brain metastases (BMs), but still, 40 % of them will experience an intracranial progression. We performed a systematic review to evaluate the role of brain radiotherapy upfront plus osimertinib. We evaluated articles comparing the use of osimertinib versus osimertinib plus brain radiotherapy.

Early taxane exposure and neurotoxicity in breast cancer patients.

Introduction: Breast cancer is the most diagnosed tumor and a leading cause of cancer death in women worldwide. Taxanes are the most used chemotherapeutic agents and are strictly connected to neurotoxicity. Taxane-induced neuropathy (TIN) significantly impacts patients' quality of life (QOL).

An Unsupervised Learning Tool for Plaque Tissue Characterization in Histopathological Images.

Stroke is the second leading cause of death and a major cause of disability around the world, and the development of atherosclerotic plaques in the carotid arteries is generally considered the leading cause of severe cerebrovascular events. In recent years, new reports have reinforced the role of an accurate histopathological analysis of carotid plaques to perform the stratification of affected patients and proceed to the correct prevention of complications. This work proposes applying an unsupervised learning approach to analyze complex whole-slide images (WSIs) of atherosclerotic carotid plaques to allow a simple and fast examination of their most relevant features.

Artificial Intelligence Models for the Detection of Microsatellite Instability from Whole-Slide Imaging of Colorectal Cancer.

With the advent of whole-slide imaging (WSI), a technology that can digitally scan whole slides in high resolution, pathology is undergoing a digital revolution. Detecting microsatellite instability (MSI) in colorectal cancer is crucial for proper treatment, as it identifies patients responsible for immunotherapy. Even though universal testing for MSI is recommended, particularly in patients affected by colorectal cancer (CRC), many patients remain untested, and they reside mainly in low-income countries.

Bone health and body composition in prostate cancer: Meet-URO and AIOM consensus about prevention and management strategies.

Background: Prostate cancer (PCa) treatments are associated with a detrimental impact on bone health (BH) and body composition. However, the evidence on these issues is limited and contradictory. This consensus, based on the Delphi method, provides further guidance on BH management in PCa.

CD44: A New Prognostic Marker in Colorectal Cancer?

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial-mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy.

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging.

Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes.

Primary adrenal insufficiency induced by immune checkpoint inhibitors: biological, clinical, and radiological aspects.

Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, with evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges.

CDK4/6 inhibition in hormone receptor-positive/HER2-negative breast cancer: Biological and clinical aspects.

A dysregulated cell division, one of the key hallmarks of cancer, results in uncontrolled cellular proliferation. This aberrant process, mediated by a dysregulated cell-cycle machinery and overactivation of cyclin-dependent kinase (CDK) 4 and 6, can potentially promote tumorigenesis. The clinical application of CDK 4/6 inhibitors, developed to inhibit cell-cycle progression, in the treatment regimens of breast cancer (BC) patients is expanding.

Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN.

Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research.

Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy.

Background: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC).

Methods: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona.