Oncologic Anthropology and the African Diaspora: Twenty-Year Anniversary Report, International Center for the Study of Breast Cancer Subtypes (ICSBCS).

The International Center for the Study of Breast Cancer Subtypes (ICSBCS) has played a vital role in defining and overcoming many inequities that exist in breast cancer treatment and outcome on a global basis through capacity-building programs that improve the management of breast cancer patients across the African diaspora. ICSBCS activities also fill critical gaps in disparities research related to the genetics of ancestry. Over the past 20 years, ICSBCS teams have spearheaded landmark studies documenting the relevance of genetic African ancestry to breast cancer risk, while also improving the quality of care delivered to patients in diverse communities.

Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model.

Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs.

Exosomal ALPPL2 and THBS2 as biomarkers for early detection and disease monitoring of pancreatic ductal adenocarcinoma.

Background: Lack of reliable biomarkers for early detection and monitoring contributes to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), as the current clinical marker, CA19-9, lacks adequate specificity and sensitivity.

Methods: Serum concentrations of ALPPL2-positive and THBS2-positive exosomes were measured using an ExoView assay in two cohorts: a cohort of 219 subjects, including non-disease controls and patients with early- or late-stage PDAC, and a longitudinal cohort of 26 patients with advanced PDAC undergoing treatment.

Results: Exosomal ALPPL2 and THBS2 distinguished non-cancer cases from PDAC with high accuracy; area under the curve (AUC) values = 0.

Real-world progression-free survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR-positive/HER2-negative metastatic breast cancer in United States routine clinical practice.

Background: All three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, and abemaciclib) plus aromatase inhibitor (AI) significantly prolonged progression-free survival (PFS) versus placebo plus AI and achieved a similar reduction in risk of disease progression in randomized controlled trials (RCTs) evaluating first-line (1L) treatment of hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). To date, there have been no head-to-head RCT data comparing CDK4/6i, and most real-world comparative effectiveness studies were limited by small sample sizes and/or short follow-up. In this analysis, we compared real-world PFS (rwPFS) in patients with HR-positive/HER2-negative mBC receiving 1L CDK4/6i plus AI in United States routine clinical practice.

Tumor-derived EBI3 promotes CD8+ T cell exhaustion via STAT4-IL-10/CCL5 in gastric cancer.

Combination chemotherapy and immunotherapy are effective against advanced gastric cancer (GC). However, T cell exhaustion in the tumor microenvironment may decrease the immune response and compromise the effectiveness of immunotherapy. Herein, we report the potential role of EBI3 in promoting T cell exhaustion and its mechanism in GC, showing high expression of EBI3 in GC.

Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8 T cells.

Neutrophils have emerged as key players in tumor progression and are often associated with poor prognosis. Despite ongoing efforts to target neutrophil functions in cancer, therapeutic success has been limited. In this study, we addressed the possibility of blocking STAT3 signaling in neutrophils as a targeted therapeutic intervention in cancer.

Precision Oncology Through Dialogue: AI-HOPE-RTK-RAS Integrates Clinical and Genomic Insights into RTK-RAS Alterations in Colorectal Cancer.

The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes-including KRAS, NRAS, BRAF, and EGFR-are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks.

Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.

Background: Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma.

Patients And Methods: Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated.

Pathway-Specific Genomic Alterations in Pancreatic Cancer Across Populations at Risk.

Pancreatic cancer (PC) is a highly aggressive malignancy with increasing incidence and poor survival. Hispanic/Latino (H/L) patients, despite having a lower overall incidence than Non-Hispanic White (NHW) patients, are often diagnosed younger and at more advanced stages, leading to worse outcomes. The molecular mechanisms underlying these disparities remain unclear.

The immunophenotypic and genetic characterization of pediatric T -L ymphoblastic leukemia with a mature immunophenotype.

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Efficacy and safety of one-time autologous tumor-infiltrating lymphocyte cell therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Background: Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a high recurrence rate after first-line immunotherapy or chemoimmunotherapy. The presence of a high density of tumor-infiltrating lymphocytes (TILs) in HNSCC tumors was shown to be associated with improved clinical outcomes. One-time autologous TIL cell therapy was evaluated in patients with recurrent and/or metastatic HNSCC.

Conversational AI agent for precision oncology: AI-HOPE-WNT integrates clinical and genomic data to investigate WNT pathway dysregulation in colorectal cancer.

Introduction: The WNT signaling pathway is a key driver of colorectal cancer (CRC) initiation and progression, particularly in early-onset CRC (EOCRC) among underserved populations. However, interrogating WNT pathway dysregulation across clinical and genomic dimensions remains technically challenging, limiting both translational insight and personalized intervention strategies. To address this gap, we developed AI-HOPE-WNT, the first conversational artificial intelligence (AI) agent purpose-built to investigate WNT signaling in CRC using natural language-driven, integrative bioinformatics.

Ten-year survival rates by PSA nadir in patients with metastatic hormone-sensitive prostate cancer: long-term survival analysis from the ECOG-ACRIN 3805 (CHAARTED) trial.

Background: The CHAARTED trial investigated the long-term survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) with or without docetaxel (D). This analysis focuses on 10-year overall survival (OS) stratified by disease volume and on-therapy PSA levels at 6 months.

Methods: OS was calculated using the Kaplan-Meier method from randomization to death or last known alive date.

Quantitative Evaluation of AI-based Organ Segmentation Across Multiple Anatomical Sites Using Eight Commercial Software Platforms.

Purpose: To evaluate organs-at-risk (OARs) segmentation variability across eight commercial AI-based segmentation software using independent multi-institutional datasets, and to provide recommendations for clinical practices utilizing AI-segmentation.

Methods: 160 planning CT image sets from four anatomical sites: head-and-neck, thorax, abdomen and pelvis were retrospectively pooled from three institutions. Contours for 31 OARs generated by the software were compared to clinical contours using multiple accuracy metrics, including: Dice similarity coefficient (DSC), 95 Percentile of Hausdorff distance (HD95), surface DSC, as well as relative added path length (RAPL) as an efficiency metric.

Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis.

A pro-tumorigenic role for adipocytes has been identified in breast cancer, and reliance on fatty acid catabolism found in aggressive tumors. The molecular mechanisms by which tumor cells coopt neighboring adipocytes, however, remain incompletely understood. Here, we describe a direct interaction linking tumorigenesis to adjacent adipocytes.

Immunotherapy in Renal Cell Carcinoma.

There have been tremendous advancements in immunotherapy approaches for patients with renal cell carcinoma (RCC) from the initial interleukin-2 era to the current immune checkpoint inhibitor (ICI) combinations. Several ICI-based therapies have greatly improved outcomes for patients with RCC with the potential for durable responses for a subset of patients. In this chapter, we review the data of key frontline ICI-based combinations for RCC in the metastatic setting and recent data on adjuvant immunotherapy.

Pancreatic Cancer Immunotherapy: A Team-Based Approach.

Immunotherapeutic approaches have created effective therapy with a manageable toxicity profile as a new treatment approach in a wide variety of cancers, often leading to longer responses and control of disease. In pancreatic cancer, responses to immunotherapy have been difficult to capture. Many obstacles have been identified in the limited efficacy of immunotherapy in pancreatic cancers.

Immunotherapy in Melanoma.

This chapter explores systemic treatment strategies for cutaneous melanoma across neoadjuvant, adjuvant, and Stage IV settings. Neoadjuvant therapy aims to reduce tumor burden pre-surgery, primarily using immune checkpoint inhibitors like nivolumab plus ipilimumab, showing promising response rates. Adjuvant therapy, post-resection, leverages immunotherapy (e.

Breast Cancer Immunotherapy: A Team Science Approach.

Immunotherapy has reshaped the treatment landscape of several malignancies, including breast cancer. While historically considered less immunogenic, breast cancer-particularly the triple-negative subtype (TNBC)-has demonstrated responsiveness to immune checkpoint inhibitors (ICIs). TNBC is characterized by higher tumor mutational burden, elevated PD-L1 expression, and increased tumor-infiltrating lymphocytes, making it a leading focus of immunotherapy development.

Recent Advancements in Immunotherapy for the Treatment of Metastatic Breast Cancer.

Breast cancer (BC) is the most prevalent malignancy among women in the United States, affecting approximately 13% of the female population. While advancements in treatment strategies have improved survival rates, significant challenges remain due to tumor heterogeneity, metastatic progression, and acquired resistance to therapy. Recent studies have highlighted the potential of immunotherapy in managing various solid tumors, including BC.

Identifying Patients With Low Relapse Rate Despite High-Risk Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: Development and Validation of a Clinicopathologic Assay.

Purpose: Escalation of adjuvant systemic therapies (eg, with cyclin-dependent kinase 4 and 6 inhibitors) is now indicated for patients with clinically defined high-risk estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer, although it is unclear which will benefit from additional therapies. We developed and validated a prognostic clinicopathologic assay identifying a subpopulation of high-risk patients with good prognosis after standard adjuvant therapies, who may safely forgo treatment escalation.

Methods: We trained a Cox proportional-hazards model that integrates clinicopathologic variables with features derived from digitized hematoxylin-and-eosin-stained resection slides from a retrospective data set.

Clinical and Pathological Predictors for Occult Lymph Node Involvement in Patients With Clinical Node-Negative Bladder Cancer Undergoing Radical Cystectomy.

Background: Occult pathological lymph node involvement in patients with clinical node-negative (cN0) bladder cancer (BC) remains a diagnostic challenge. We evaluate predictors of lymph node positivity (pN+) in patients with cT1-4N0M0 BC undergoing radical cystectomy and pelvic lymph node dissection (RC-PLND).

Methods: We included patients with cT1-4N0M0 BC undergoing RC-PLND from February 2004 through October 2020.

MechanoAge, a machine learning platform to identify individuals susceptible to breast cancer based on mechanical properties of single cells.

Background: Existing breast cancer risk models inadequately identify individuals at latent risk, particularly among women without known genetic mutations or family history. Risk is often underestimated or overestimated due to reliance on population-level data and neglect of cellular aging and mechanobiological alterations.

Methods: We profiled primary human mammary epithelial cells (HMECs) from women of varying ages and risk backgrounds using mechano-node-pore sensing (mechano-NPS), a high-throughput microfluidic platform that captures single-cell mechanical properties.

Development of a Health-related Quality of Life Questionnaire for Patients with Metastatic or Localized Renal Cell Carcinoma.

Background And Objective: Despite significant advances in treatments for renal cell carcinoma (RCC) over the past decade, health-related quality of life (HRQOL) assessments have not been updated to reflect these developments. The aim of our study was to refine assessment of HRQOL for patients with localized or metastatic RCC.

Methods: We conducted a four-phase international study (August 2022-October 2024).