Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study.

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.

Patients And Methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers.

Antibody-drug conjugates in metastatic breast cancer: sequencing, combinations and resistances.

Purpose Of Review: Significant advancements have been made in treating metastatic breast cancer (MBC) with antibody drug conjugates (ADCs). However, due to the development of resistance, patients experience disease progression. The aim of this review is to summarize current evidence on ADCs sequencing strategies and combination approaches in the treatment of MBC.

Biomimetic Approaches in Scaffold-Based Blood Vessel Tissue Engineering.

Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes.

Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.

Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.

Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) have reshaped the cancer treatment landscape across a variety of different tumor types. ADCs' peculiar pharmacologic design combines the cytotoxic properties of chemotherapeutic agents with the selectivity of targeted therapies. At present, the approval of many ADCs used in clinical practice has not always been biomarker-driven.

The evolving landscape of metastatic HER2-positive, hormone receptor-positive Breast Cancer.

Therapeutic agents targeting Human Epidermal Growth Factor Receptor 2 (HER2) demonstrated to positively impact the prognosis of HER2-positive breast cancer. HER2-positive breast cancer can present either as hormone receptor-negative or positive, defining Triple-positive breast cancer (TPBC). TPBC demonstrate unique gene expression profiles, showing reduced HER2-driven gene expression, as recapitulated by a higher proportion of Luminal-type intrinsic subtypes.

Light-responsive polymeric nanoparticles for retinal drug delivery: design cues, challenges and future perspectives.

A multitude of sight-threatening retinal diseases, affecting hundreds of millions around the globe, lack effective pharmacological treatments due to ocular barriers and common drug delivery limitations. Polymeric nanoparticles (PNPs) are versatile drug carriers with sustained drug release profiles and tunable physicochemical properties which have been explored for ocular drug delivery to both anterior and posterior ocular tissues. PNPs can incorporate a wide range of drugs and overcome the challenges of conventional retinal drug delivery.

Neoadjuvant therapy in hormone Receptor-Positive/HER2-Negative breast cancer.

Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making.

Mending a broken heart by biomimetic 3D printed natural biomaterial-based cardiac patches: a review.

Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary.

Targeting HER2 heterogeneity in breast and gastrointestinal cancers.

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors.

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study.

Background: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases.

Methods: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases.

Resistance to Antibody-Drug Conjugates Targeting HER2 in Breast Cancer: Molecular Landscape and Future Challenges.

The treatment of HER2-positive metastatic breast cancer (mBC) with Trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd), two antibody-drug conjugates (ADCs) targeting HER2, is burdened by progression of disease related to the acquisition of mechanisms of resistance. Resistance to T-DM1 is caused by the decrease of HER2 expression, the alteration of intracellular trafficking, the impairment of lysosome functions, the drug expulsion through efflux pumps and the activation of alternative signal pathways. Instead, the decrease of HER2 expression and loss of function mutations represent the first evidences of mechanisms of resistance to T-DXd, according to the results of DAISY trial.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia.

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown.