Activity of Platinum Chemotherapy in Men With Prostate Cancer With and Without DNA Damage Repair Mutations.

Introduction: Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR.

A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.

Qualitative assessment of proposed visual key information pages for informed consent.

Introduction: The 2018 Common Rule revision intended to improve informed consent by recommending a concise key information (KI) section, yet provided little guidance about how to describe KI. We developed innovative, visual KI templates with attention to health literacy and visual design principles. We explored end users' attitudes, beliefs, and institutional policies that could affect implementing visual KI pages.

Cancer-related health behaviors during the COVID 19 pandemic in geographically diverse samples across the US.

Background: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors.

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.

Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.

Evaluating ovarian cancer risk-reducing salpingectomy acceptance: a survey.

With evidence that salpingectomy is effective in preventing high grade serous carcinoma, it is time to consider offering this procedure to people at higher-than-average lifetime risk for ovarian cancer, despite not having a pathogenic genetic variant that increases risk for ovarian cancer. This targeted approach has potential to be effective at reducing ovarian cancer incidence, and unlike opportunistic salpingectomy is focused on people with an increased lifetime risk of ovarian cancer. However, the acceptability of this approach within the population of potential patients remains unknown.

KRAS Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma.

Importance: Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC.

Objective: To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations.

Timing of Resistance Exercise and Cardiometabolic Outcomes in Adults with Prediabetes: A Secondary Analysis.

The objective of this study was to explore if the time of day (AM vs PM) resistance exercise is performed influences glucose and insulin concentrations, body composition, and muscular strength in adults with prediabetes. A secondary data analysis was conducted using data from the "Resist Diabetes" study, a phase II exercise intervention. Participants (Age:59.

Intrauterine Growth Restriction Alters Postnatal Hippocampal Dentate Gyrus Neuron and Microglia Morphology and Cytokine/Chemokine Milieu in Mice.

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation.

A multi-constraint Monte Carlo Simulation approach to downscaling cancer data.

This study employs an innovative multi-constraint Monte Carlo simulation method to estimate suppressed county-level cancer counts for population subgroups and extend the downscaling from county to ZIP Code Tabulation Areas (ZCTA) in the U.S. Given the known cancer counts at a higher geographic level and larger demographic groups at the same geographic level as constraints, this method uses the population structure as probability in the Monte Carlo simulation process to estimate suppressed data entries.

The Association Between Body Composition, Overall Survival, Treatment Decisions, and Patient-Reported Outcomes in Metastatic Non-Small-Cell Lung Cancer.

Introduction: The purpose of this study was to evaluate the association between body composition, overall survival, odds of receiving treatment, and patient-reported outcomes (PROs) in individuals living with metastatic non-small-cell lung cancer (mNSCLC).

Methods: This retrospective analysis was conducted in newly diagnosed patients with mNSCLC who had computed-tomography (CT) scans and completed PRO questionnaires close to metastatic diagnosis date. Cox proportional hazard models and logistic regression evaluated overall survival and odds of receiving treatment, respectively.

A precision oncology-focused deep learning framework for personalized selection of cancer therapy.

Precision oncology matches tumors to targeted therapies based on the presence of actionable molecular alterations. However, most tumors lack actionable alterations, restricting treatment options to cytotoxic chemotherapies for which few data-driven prioritization strategies currently exist. Here, we report an integrated computational/experimental treatment selection approach applicable for both chemotherapies and targeted agents irrespective of actionable alterations.

Discrimination, Violence, Mental Health, and Substance Use by Age and Cancer History Among LGBTQ+ Individuals.

Young adult (YA) LGBTQ+ cancer survivors face inequities and unmet needs that impact their well-being. However, the impact of age and cancer among LGBTQ+ individuals have not been adequately assessed. The North Carolina LGBTQ+ Health Needs Assessment survey, conducted at local Pride events, aimed to collect data to describe the well-being of LGBTQ+ people in NC.

Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients.

Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies.

Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings.

SLC7A5 is required for cancer cell growth under arginine-limited conditions.

Tumor cells must optimize metabolite acquisition between synthesis and uptake from a microenvironment characterized by hypoxia, lactate accumulation, and depletion of many amino acids, including arginine. We performed a metabolism-focused functional screen using CRISPR-Cas9 to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter.

Comorbid conditions and survival among Black women with ovarian cancer.

Background: Black women with epithelial ovarian cancer (EOC) have worse survival and a higher burden of comorbid conditions compared with other racial groups. This study examines the association of comorbid conditions and medication use for these conditions with survival among Black women with EOC.

Methods: In a prospective study of 592 Black women with EOC, the Charlson comorbidity index (CCI) based on self-reported data, three cardiometabolic comorbidities (type 2 diabetes, hypertension, and hyperlipidemia), and medication use for each cardiometabolic comorbidity were evaluated.

Examining Bi-directional links between distinct affect states and tobacco lapse during a cessation attempt.

Background: Theoretical models of addiction highlight the bi-directional links of certain distinct affect states and tobacco lapse, but to date, few studies have examined bi-directional associations, instead examining associations with global affect measures (e.g., negative affect versus feelings of guilt).

Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation.

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation.

A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer.

Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).

Real-world Effectiveness of Single-Agent Enfortumab Vedotin in Patients With Advanced Urothelial Carcinoma.

Background: Enfortumab vedotin (EV) is a nectin-4-directed antibody and microtubule inhibitor conjugate indicated for patients with metastatic urothelial carcinoma (mUC) who have received prior platinum-based chemotherapy and PD-1/L1 inhibitors or are ineligible for cisplatin-containing regimens and have undergone at least 1 prior line of therapy. EV is also indicated in combination with pembrolizumab in the first-line setting. However, real-world effectiveness of EV based on treatment line and impact of prior therapy remains unclear.