Evolutionary Overview and Future Perspectives: ESR1 Mutations, Liquid Biopsy, and Artificial Intelligence for a New Era of Personalized Medicine in ER+ Breast Cancer.

ESR1 gene mutations represent one of the main mechanisms of acquired resistance to endocrine therapy (ET) in estrogen receptor-positive (ER+) breast cancer. The introduction of liquid biopsy as a minimally invasive technique for analyzing circulating tumor DNA (ctDNA) has opened new avenues for real-time mutation monitoring and personalized treatment strategies. This review explores the clinical relevance of ESR1 mutations in endocrine resistance, the potential of liquid biopsy for early detection and monitoring, and the integration of advanced sequencing technologies and artificial intelligence to improve diagnostic accuracy.

Impact of antibiotic therapy in patients with cholangiocarcinoma treated with chemoimmunotherapy.

Background: Patients with biliary tract cancers (BTC) often require antibiotic therapy before starting systemic treatment that includes an immune checkpoint inhibitor. This study aims to evaluate the prognostic impact of antibiotic therapy administered in the 15 days prior to the start of chemoimmunotherapy in patients with BTC.

Material And Methods: The study population included patients with metastatic or locally advanced BTC from western and eastern populations treated with first-line chemoimmunotherapy.

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.

Integrating tissue and liquid biopsy comprehensive genomic profiling to predict efficacy of anti-EGFR therapies in metastatic colorectal cancer: Findings from the CAPRI-2 GOIM study.

Introduction: We investigated the role of integrating tissue biopsy (TBx)- and liquid biopsy (LBx)-comprehensive genomic profiling (CGP) to predict the activity of FOLFIRI plus cetuximab.

Methods: The CAPRI-2 GOIM study is a non-randomized phase 2 study evaluating a biomarker-driven anti-EGFR treatment in three lines of therapy in patients with RAS/BRAF wild type metastatic colorectal cancer. At baseline, TBx and LBx were analyzed using the FoundationOne CDx platform.

Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real-life worldwide population.

In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real-world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD.

The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine and durvalumab: a large real-life worldwide population.

Background & Aims: Cisplatin, gemcitabine, and durvalumab (CGD) combination is a standard first-line treatment for advanced biliary tract cancer (BTC). This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced BTC treated with CGD in real-world clinical practice.

Methods: Patients with unresectable, locally advanced, or metastatic BTC treated with CGD across 39 centers in 11 countries (Europe, United States, and Asia) were included in this analysis.

A Prognostic Index for Advanced Biliary Tract Cancer Treated With Cisplatin, Gemcitabine and Durvalumab: The MAGIC-D Index.

Background: Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first-line setting.

Patients And Methods: The study population consisted of patients with BTC from 11 Eastern and Western Countries.

Exercise Prescription in Cardio-Oncology.

Numerous studies underscore the benefits of exercise prescription in both cardiology and oncology. Recently, emerging eviAlessandro Navadence has highlighted the value of exercise in cardio-oncology, demonstrating its protective effects against the decline in functional capacity and cardiovascular complications that may arise in oncology patients, either as a result of the disease itself or as a side effect of chemotherapy. The purpose of this review is to elucidate the protective mechanisms and cardiovascular clinical benefits conferred by exercise prescription in cancer patients.

Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population.

Background: The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (A + B) or with Lenvatinib.

Methods: The study population included patients affected with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma not suitable for locoregional therapies (LRTs) from eastern and western populations, who received atezolizumab plus bevacizumab (A + B) or Lenvatinib as first-line treatment. Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and time to progression (TTP) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model.

The interplay between gut microbiota, antibiotics, and immune checkpoint inhibitors in patients with cancer: A narrative review with biological and clinical aspects.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways have revolutionized cancer therapy. However, primary and secondary resistance to ICI pose significant challenges. Recent studies underscore the critical role of gut microbiota (GM) in modulating ICI efficacy by shaping host immune responses and regulating the tumor microenvironment (TME).

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.

Factors associated with reaching maintenance therapy in patients with advanced biliary tract cancer treated with durvalumab: Real-world results from a multicenter and multinational study.

Standard of care first-line systemic treatment for advanced biliary tract cancer includes chemo-immunotherapy with gemcitabine, cisplatin, and durvalumab, followed by maintenance durvalumab monotherapy. The present work aims to investigate the differences in baseline clinical and molecular characteristics between patients with early progression during chemo-immunotherapy and those who reach durvalumab maintenance therapy. The study population included patients with unresectable, locally advanced, or metastatic BTC who received treatment at 38 clinical Institutions in 12 countries from July 2021 to December 2023.

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.

Exploring the Prognostic and Predictive Impact of Genomic Loss of Heterozygosity and Homologous Recombination Deficiency Alterations in Patients With Metastatic Colorectal Cancer.

Purpose: Genomic loss-of-heterozygosity (gLOH) consists in the loss of chromosomal regions and is associated with homologous recombination repair (HRR) system deficiency. We explored the role of gLOH and HRR-related gene alterations in metastatic colorectal cancer (mCRC).

Methods: FoundationOne CDx assay was used to determine the percentage of gLOH and the presence of alterations in 27 HRR-related genes in archival chemo-naïve tumor tissues of patients with mCRC treated with first-line oxaliplatin- or irinotecan-based doublets and triplet ± anti-PD-L1.

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.

Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics.

The integrity of p53 machinery is crucial for platinum activity, while p53 mutation is frequent in high-grade serous ovarian cancer (HGS-OC). This study aimed to evaluate the link between p53 mutations, platinum sensitivity (PS), and the platinum-free interval (PFI) in patients with HGS-OC. We prospectively analyzed 159 consecutive women with ovarian cancer who underwent surgery.

Trifluridine/tipiracil regimen in combination with bevacizumab for metastatic colorectal cancer in the third line: an expert opinion.

The prolongation of survival along with the preservation of quality of life, possibly avoiding harmful cumulative toxicities, is the primary therapeutic aim for patients with metastatic colorectal cancer (mCRC) in the third-line setting. Several therapeutic options are now available, although some differences across countries in drug approval and the optimal therapeutic sequencing associated with each peculiar patient subgroup represent a clinical challenge for oncologists. Among various options, the SUNLIGHT trial showed how the combination of trifluridine/tipiracil (FTD/TPI) with bevacizumab is effective with an easily manageable toxicity profile compared to FTD/TPI alone.

Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants.

Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.

Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.

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.

Chemotherapy plus immunotherapy as first line combination in older patients with extensive stage small cell lung cancer: A systematic review and meta-analysis.

Background: Small-cell lung cancer (SCLC) accounts for 10%-15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC.

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.

"Artificial histology" in colonic Neoplasia: A critical approach.

Background: The histological assessment of colorectal precancer and cancer lesions is challenging and primarily impacts the clinical strategies of secondary colon cancer prevention. Artificial intelligence (AI) models may potentially assist in the histological diagnosis of this spectrum of phenotypical changes.

Objectives: To provide a current overview of the evidence on AI-based methods for histologically assessing colonic precancer and cancer lesions.

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.

Viral Hepatitis in Western Patients with Advanced Intrahepatic Cholangiocarcinoma: Retrospective Assessment of Prevalence, Prognostic and Predictive Significance.

Despite a biologically established causative role of viral hepatitis (VH), i.e. HBV and HCV infections, on intrahepatic cholangiocarcinoma (ICC), only few large Western cohorts exploring the association between VH and ICC development are available.