ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics.

Activated CDC42-associated kinase 1 (ACK1), encoded by the TNK2 gene, is a cytoplasmic non-receptor tyrosine kinase whose aberrant activation correlates positively with cancer severity. Recent research has revealed the functional relevance of this oncokinase - it is an epigenetic regulator that drives cancer progression in multiple malignancies. Although ACK1 is an attractive target for therapeutic intervention, incomplete knowledge of its diverse signaling mechanisms and the lack of specific inhibitors have challenged its clinical success.

Large Bilobed Flap for Head and Neck Reconstruction: Technique and Outcomes.

Background: Head and neck reconstruction after resection of cutaneous malignancies spans the entire reconstructive ladder. Local flaps, such as the bilobed flap, offer excellent versatility, negligible morbidity, and minimal hospitalization. However, there is sparse data regarding the bilobed flap for large defects of the head and neck.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to individual agents cannot be easily delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

BioMedGraphica: An All-in-One Platform for Biomedical Prior Knowledge and Omic Signaling Graph Generation.

Artificial intelligence (AI) is revolutionizing scientific discovery because of its super capability, following the neural scaling laws, to integrate and analyze large-scale datasets to mine knowledge. Foundation models, large language models (LLMs) and large vision models (LVMs), are among the most important foundations paving the way for general AI by pre-training on massive domain-specific datasets. Different from the well annotated, formatted and integrated large textual and image datasets for LLMs and LVMs, biomedical knowledge and datasets are fragmented with data scattered across publications and inconsistent databases that often use diverse nomenclature systems in the field of AI for Precision Health and Medicine (AI4PHM).

Challenges and Supports for Implementing Health Equity During National Accreditation Among Small Local Health Departments in the United States.

Objective: This article focuses on supports and challenges to health equity that small local health departments (LHDs) experienced while working toward national reaccreditation or Pathways Recognition with the Public Health Accreditation Board's Standards & Measures Version 2022 (PHAB S&M v2022).

Design: The study team conducted 22 qualitative interview sessions with members of health department leadership teams.

Setting: In the spring of 2024, participants from 4 small LHDs in the western and midwestern regions of the United States participated in individual remote interview sessions.

Performance of PSMA-PET/CT as verified by bone biopsy for diagnosing osseous metastases of prostate cancer.

Objective: Prostate-specific membrane antigen (PSMA)-PET/CT has shown considerable promise in the evaluation of prostate cancer bone metastases; however, data utilizing a histopathologic reference standard in this setting are limited. We therefore sought to evaluate the diagnostic performance of PSMA-PET/CT using a consistent histopathologic gold standard in the form of bone biopsy.

Materials And Methods: In this single-center, retrospective study, we identified 80 patients with prostate cancer who underwent CT-guided bone biopsy of a tracer-avid osseous lesion on PSMA-PET/CT performed with F-piflufolastat.

Long-Term Follow-Up and Overall Survival in NRG258, a Randomized Phase III Trial of Chemoradiation Versus Chemotherapy for Locally Advanced Endometrial Carcinoma.

This randomized phase III trial aimed to determine whether treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for four cycles (chemoradiotherapy [C-RT]) increased recurrence-free survival (RFS) and overall survival (OS) when compared with carboplatin and paclitaxel for six cycles (chemotherapy [CT]) in locally advanced endometrial cancer (UC). Previously reported results showed that C-RT did not improve RFS compared with CT. Here we report the final OS analysis.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

NCCN Guidelines® Insights: Survivorship, Version 2.2024.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

Education and mammographic breast density.

Purpose: There are conflicting reports on the associations of education with mammographic breast density (MBD). To address this, we investigated the associations of education with MBD and additionally determined if and to what extent this association is mediated by known confounders such as age and adiposity.

Methods: Women (n = 1155) were recruited during their annual screening mammogram at the Joanne Knight Breast Health Center at Washington University School of Medicine in St.

Effectiveness and Safety of Irreversible Electroporation When Used for the Ablation of Stage 3 Pancreatic Adenocarcinoma: Initial Results from the DIRECT Registry Study.

Background/objectives: Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study.

Systemic Therapy for Stage I-III Anal Squamous Cell Carcinoma: ASCO Guideline.

Purpose: To provide evidence-based guidance for clinicians who treat patients with stage I-III anal cancer.

Methods: A systematic review of the literature conducted by the Minnesota Evidence-based Practice Center provided the evidence base for this guideline. An ASCO Expert Panel reviewed this evidence and came to consensus on a set of evidence-based recommendations.

Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial.

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D vs. placebo.

Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data.

Background: Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged <50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.

Methods: Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO-International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database.

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy. Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes, Bmal1 and Cry.

SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers.

Purpose: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

Methods: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m, cisplatin 25 mg/m, and nab-paclitaxel 100 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m and cisplatin 25 mg/m intravenously once per day on days 1 and 8 of a 21-day cycle).

Results: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC.

T cell dynamics with neoadjuvant immunotherapy in head and neck cancer.

Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies.

Allostatic Load, Educational Attainment, and Risk of Cancer Mortality Among US Men.

Importance: Health disparities among racial and ethnic minoritized populations, particularly for cancer mortality rates, remain a major public health concern. Men from underrepresented backgrounds (Black and Hispanic men, specifically) face the pervasive effects of discrimination in their daily lives, which also contribute to the complex associations among allostatic load (a marker of chronic stress), educational opportunities, and elevated risks of cancer mortality.

Objective: To elucidate the associations among educational attainment, allostatic load, and cancer mortality risk among men.

Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA.

JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.

Sequencing bispecific antibodies and CAR T cells for FL.

Treatment for relapsed/refractory (R/R) follicular lymphoma (FL) has evolved over recent years with the introduction of multiple novel immunotherapies: anti-CD3  ×  CD20 bispecific antibody (BsAb) T-cell engagers and anti-CD19 chimeric antigen receptor T cells (CAR T). Both drug classes are highly active, and their adverse event profiles overlap considerably, with cytokine release syndrome, cytopenias, and infections being most common. However, key differences include accessibility and logistical considerations as well as distinct neurologic toxicities, which make recommending a BsAb or CAR T a nuanced decision for each patient with R/R FL.

Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial.

Background: The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.

Methods: The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries.

Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer.

Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance.

The Untapped Opportunities of Addressing Lifecourse Growth in Mammographic Breast Density and Breast Cancer Prevention in Non-Hispanic Black Women.

This commentary discusses the importance of adiposity and lifecourse growth with mammographic breast density (MBD) in non-Hispanic Black (NHB) women. Although high MBD is a well-established risk factor for breast cancer, the determinants of MBD in NHB women remain understudied. Although adiposity at the time of mammography is most strongly associated with MBD, adiposity as early as ages 10 and 18 years is also independently associated with MBD.