The International Classification of Diseases for Oncology, 4th Edition (ICD-O-4): An overview.

Alteration in gene expression patterns and increased drug resistance in MCF7 breast cancer cells cultured on 3D collagen-based scaffolds.

From slides to AI-ready maps: Standardized multi-layer tissue maps as metadata for artificial intelligence in digital pathology.

Cisplatin disrupts OCT1-DNMT1-piRNA epigenetic regulatory axis to suppress GAB2-mediated aggressiveness in OSCC.

Millimeter-scale, high-density three-dimensional constructs recapitulate hot and cold tumor microenvironment.

Intravesical hematoporphyrin photodynamic therapy combined with pirarubicin for intermediate and high-risk non-muscle-invasive bladder cancer: A multicenter, prospective single-arm cohort.

A qualitative study of patient perspectives for a mindfulness-based intervention in lung cancer.

Evidence from tumor neuroscience and clinical observations have implicated the autonomic nervous system (ANS) in breast cancer pathobiology. Sympathetic activation (norepinephrine/β-adrenergic signaling) aligns with pro-angiogenic, pro-invasive programs and distant spread, whereas increased vagal activity is associated with an anti-inflammatory state and restraint of progression. The present review summarizes mechanistic, translational and clinical data supporting a bidirectional regulatory model and evaluates a variety of ANS-targeted strategies, including β-adrenergic modulation, non-invasive vagus nerve stimulation and related neuromodulatory approaches. Whilst biologic plausibility is strong, clinical evidence remains heterogeneous and limited by study design. To the best of our knowledge, no adequately powered randomized trials have demonstrated sufficient survival benefits. The present review outlines principles for standardized autonomic phenotyping (such as heart rate variability), candidate patient selection and trial endpoints to test whether ANS modulation can improve recurrence, metastasis, toxicity and quality-of-life outcomes. Through integrating convergent evidence and articulating testable hypotheses, the present review provides an ANS-informed framework to guide future breast cancer research and care.

Introduction: Postoperative pain management is of prime importance to the surgeon, as it significantly influences a patient’s recovery. A multimodal approach to pain management is an essential component of postoperative care. Curcumin, a natural antioxidant and anti-inflammatory compound, also exhibits analgesic properties. However, its use in the postoperative setting has not been extensively studied. Aim: To evaluate the role of oral curcumin as an analgesic in the management of postoperative pain following breast cancer surgery. Materials and Methods: This was a single-blind, randomised controlled trial that was conducted in the Department of Surgical Oncology, Cancer Research Institute, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India and included 60 patients undergoing surgery for breast cancer between October 2023 and April 2024. The study group was administered oral curcumin lozenges twice daily, along with standard analgesics, from Postoperative Day (POD) 1. The control group received a placebo. Postoperative pain was assessed from POD 0 to POD 7 using the 11-point Numeric Pain Scale (NPS) and compared using the independent t-test performed with the Statistical Package for the Social Sciences (SPSS) version 25.0. Results: Sixty patients were enrolled (30 in each group). One patient in the study group was excluded from the final analysis as the study protocol was not followed; therefore, 59 patients were analysed. A statistically significant difference in pain scores between the study and control groups was observed on POD 6 and POD 7 (p-value=0.006). No significant difference was observed between the groups regarding the use of SOS analgesics (p-value=0.322) or drain output (p-value>0.05). No adverse events were reported by any patient in the study group. Conclusion: This study demonstrated that curcumin may be beneficial in postoperative pain management. The use of a nutraceutical such as curcumin, with its favourable safety profile and minimal side-effects, offers a promising option. A longer follow-up period is warranted to fully explore the analgesic potential of curcumin. Additionally, studies employing a doubleblind design and larger sample sizes are recommended to provide further evidence of its effectiveness in postoperative pain management.

Protective Effect of Docosahexaenoic Acid Supplementation during Pregnancy against Lipopolysaccharide-Induced Intrauterine Growth Restriction in Fetal Mice.

Introduction: Postoperative pain management is of prime importance to the surgeon, as it significantly influences a patient’s recovery. A multimodal approach to pain management is an essential component of postoperative care. Curcumin, a natural antioxidant and anti-inflammatory compound, also exhibits analgesic properties. However, its use in the postoperative setting has not been extensively studied. Aim: To evaluate the role of oral curcumin as an analgesic in the management of postoperative pain following breast cancer surgery. Materials and Methods: This was a single-blind, randomised controlled trial that was conducted in the Department of Surgical Oncology, Cancer Research Institute, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India and included 60 patients undergoing surgery for breast cancer between October 2023 and April 2024. The study group was administered oral curcumin lozenges twice daily, along with standard analgesics, from Postoperative Day (POD) 1. The control group received a placebo. Postoperative pain was assessed from POD 0 to POD 7 using the 11-point Numeric Pain Scale (NPS) and compared using the independent t-test performed with the Statistical Package for the Social Sciences (SPSS) version 25.0. Results: Sixty patients were enrolled (30 in each group). One patient in the study group was excluded from the final analysis as the study protocol was not followed; therefore, 59 patients were analysed. A statistically significant difference in pain scores between the study and control groups was observed on POD 6 and POD 7 (p-value=0.006). No significant difference was observed between the groups regarding the use of SOS analgesics (p-value=0.322) or drain output (p-value>0.05). No adverse events were reported by any patient in the study group. Conclusion: This study demonstrated that curcumin may be beneficial in postoperative pain management. The use of a nutraceutical such as curcumin, with its favourable safety profile and minimal side-effects, offers a promising option. A longer follow-up period is warranted to fully explore the analgesic potential of curcumin. Additionally, studies employing a doubleblind design and larger sample sizes are recommended to provide further evidence of its effectiveness in postoperative pain management.

Broadening clinical trial inclusivity of patients with lung cancer and brain metastases utilizing the Graded Prognostic Assessment (GPA): A call to action.

Prostate cancer is the most frequently identified cancer in men and remains a major cause of cancer-related deaths. Precise and prompt diagnosis is crucial for differentiating clinically relevant tumours from non-aggressive lesions and for guiding treatment choices. Multiparametric magnetic resonance imaging (mp MRI) has transformed prostate cancer detection through accurate lesion localization, risk assessment, and enhanced biopsy targeting. Fusion biopsy, integrating mp MRI results with real-time transrectal ultrasonography (TRUS), has become a highly efficient technique for sampling concerning lesions. Over the past thirty years, there have been swift advancements in the diagnosis and treatment of prostate cancer, such as multiparametric magnetic resonance imaging, positron emission tomography, robotic surgery, image-guided hypo fractionated and stereotactic radiotherapy, new anti-androgens, and radioligand therapies. This review addresses the current management of every stage of prostate cancer in view of recent advancements, allowing for comprehensive personalization of treatment, and highlights the potential of future studies to enhance results even further. In this document, we provide an extensive overview of the evidence backing the use of chemotherapy in the current management of advanced prostate cancer, focusing particularly on the application of chemotherapy for aggressive variant prostate cancer (such as neuroendocrine prostate cancer) and the integration of chemotherapy with androgen signalling inhibitors. As prostate cancer research advances quickly, producing new agents and treatment methods, chemotherapy remains vital for extending the lives of patients with advanced and metastatic prostate cancer.

ABSTRACT Objective: Cancer, characterized by uncontrolled cell proliferation and invasion into surrounding tissues, is a leading cause of global mortality. Traditional two-dimensional (2D) cell culture systems fail to adequately replicate the tumor microenvironment (TME). In contrast, three-dimensional (3D) culture systems, which better simulate cell–cell and cell–extracellular matrix (ECM) interactions, have become powerful tools in biomedical research. This study aims to compare the spheroid formation capacity of A549 lung cancer cells using three different 3D culture methods: ultra-low attachment (ULA) plates, agarose hydrogel, and the hanging drop technique. The primary objective is to identify the most effective spheroid formation method for A549 cells and to provide findings that can guide future biomedical research, particularly in cancer modeling, drug screening studies, and investigations of the tumor microenvironment.Materials and Methods: A549 cells were cultured using three different 3D culture methods: ultra-low attachment plates, agarose hydrogel, and the hanging drop method. In the ultra-low attachment method, spheroid formation was observed at cell densities of 5,000, 10,000, and 30,000 cells/ml. In the agarose hydrogel method, agarose concentrations of 1%, 1.5%, and 2% were used to evaluate cell aggregation and spheroid stability. In the hanging drop method, cells aggregated under the influence of gravity. Spheroid diameter and area were analyzed using ImageJ software.Results: In this study, the spheroid formation capacity of A549 lung cancer cells was evaluated using three different three-dimensional (3D) culture methods. The ultra-low attachment (ULA) plate method allowed cell aggregation; however, the resulting structures were not large or compact enough to be classified as spheroids. The hanging drop method showed that cells formed small clusters by day 3 but failed to develop a compact and stable spheroid structure by day 7. The agarose hydrogel method, particularly at a 2% agarose concentration, demonstrated the highest spheroid formation capacity compared to the other methods. In this method, spheroid formation began at 72 hours depending on cell density, with significant growth observed at a density of 30,000 cells/ml (p < 0.0001). Trypan Blue staining results indicated that 2% agarose and cell densities of 10,000–30,000 cells/ml provided the highest cell viability. Specifically, 4,800 viable cells were counted at a density of 30,000 cells/ml, while 3,600 viable cells were observed at 10,000 cells/ml. These findings suggest that the agarose hydrogel method, especially at 2% agarose concentration and higher cell densities, offers optimal spheroid formation and cell viability for A549 lung cancer cells.Conclusion: This study demonstrated that the agarose hydrogel method effectively promoted stable and organized spheroid formation in A549 lung cancer cells. Notably, the 2% agarose concentration was identified as the most effective condition for maintaining cell viability and optimizing spheroid size. In contrast, the ultra-low attachment (ULA) plate and hanging drop methods exhibited limited spheroid formation capacity, resulting in less compact and disorganized structures. These findings emphasize the critical role of three-dimensional (3D) cell culture methods in biomedical research, particularly for experimental tumor modeling and drug screening studies. In this context, the agarose hydrogel method, with its high spheroid formation capacity and ability to support cell viability, emerges as a promising 3D culture model that warrants further exploration in cancer research.

Abstract GPNMB (Glycoprotein non-metastatic melanoma protein B) is a canonical transcriptional target of MiT/TFE proteins (TFEB/TFE3/MITF), expressed at low levels in normal tissues but upregulated in numerous MiT/TFE-driven tumors such as translocation RCC, alveolar soft part sarcoma and MITF-driven melanoma, where it is associated with poor prognosis. CDX-011 (CR011-MMAE) is an anti-GPNMB ADC, with demonstrated efficacy in pre-clinical models of TFE3-fusion RCC. To further characterize GPNMB functionality and value as a cell-surface therapeutic target in tRCC, we engineered cell lines with genomic deletion of GPNMB via CRSIPR-Cas9 editing. Deletion of GPNMB in PRCC-TFE3 cell lines [UOK120/UOK124] significantly decreased clonogenic growth in 2D, spheroid size and viability and tumor xenograft growth in NSG mice and was associated with a decrease in phosphorylation of mTORC1 substrates [p-P70S6K, p-4EBP1]. We then examined expression of CD44, the primary receptor for GPNMB, and a tumor-associated antigen associated with poor prognosis in many cancers. Expression of CD44 and its ligand SPP1/OPN, was significantly increased in bulk RNA-Seq data from multiple transgenic models of SFPQ-TFE3, PRCC-TFE3 and ASPSCR1-TFE3, in human tRCC cases compared to normal kidney, and in SFPQ-TFE3/ PRCC-TFE3 transgenic kidney tumors and an ASPSCR-TFE3 PDX model, by immunoblotting and IHC, with increased membrane localization. shRNA-mediated depletion of CD44 profoundly and specifically decreased clonogenicity of multiple TFE3-fusion lines, with no effect seen in ccRCC lines. In conclusion, GPNMB regulates the growth of tRCC cells, potentially via an autocrine mechanism involving its receptor CD44, and targeting GPNMB-CD44 signaling may be of therapeutic benefit in tRCC. Citation Format: Kaushal Asrani, Juhyung Woo, Kewen Feng, Thiago Vidotto, Adrianna Amaral, Vikrant Palande, Jayaprakash Mandal, Eddie Imada, Christopher Thoburn, Sangeeta Ray, Huili Li, Yasser Ged, Nirmish Singla, John A. Copland, Laura Schmidt, W. Marston Linehan, Pedram Argani, Tamara Lotan. GPNMB:CD44 signaling drives tumor progression in translocation renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr B014.

Abstract Background: In the clear cell renal cell carcinoma (ccRCC) tumor microenvironment (TME), transforming growth factor-β (TGF-β) is a dominant immunosuppressive cytokine that suppresses NK metabolism, proliferation, and cytotoxicity. Rather than blocking TGFβ receptor, we hypothesized that elevated TGFβ in the ccRCC could be harnessed as a trigger to drive local, therapeutic cytokine expression. Methods: We engineered TGFβ-sensing circuits to conditionally express IL-12A3—a collagen-binding IL-12 fusion cytokine, in response to tumor derived TGFβ. The initial forward-strand designs produced TGFβ-inducible 70CAR/IL-12, but with leaky IL-12 expression. However, a bidirectional layout (sensor+IL-12A3 on the reverse, 70CAR on the forward) cut baseline IL-12 expression by ∼87% (43 vs 362 pg/mL, p=0.0019) without affecting CAR expression or NK cell function. To boost efficacy, we added constitutive IL-18 downstream of 70CAR (70CAR-12A3/18), while IL-12 remained TGFβ-regulated. Primary NK cells were transduced and assessed in vitro for activation and cytotoxicity against A498, ACHN, and CD70+ ccRCC PDXs, and in vivo in NSG-IL15 mice bearing A498 tumors. Tumor growth, NK persistence/infiltration/activation, and safety were evaluated, including body weight and day 7 serum cytokines (IL-12, IL-18, IL-1β, IL-2, IL-6, IFNγ, GM-CSF). Results: High transduction efficiency was achieved in NK cells after transduction with constructs 70CAR (45 ∼ 78%, n=8), 70CAR-12A3 (36 ∼ 62%, n=8), 70CAR-18 (41 ∼ 80%, n=8), and 70CAR-12A3/18 (27 ∼ 55% n=8) at MOI=2. 70CAR-12A3/18 NK cells secreted high IL-18 (∼1,800 pg/mL) and TGFβ-inducible IL-12 (21.6 vs 324.2 pg/mL ± TGFβ1; p=0.0013), showed enhanced cytotoxicity against A498, ACHN, and CD70+ ccRCC PDXs, and fully overcame TGFβ-mediated suppression with combined IL-12+IL-18 (either alone was insufficient). In NSG-IL15 mice subcutaneously implanted with A498 tumors, 70CAR-12A3/18 significantly reduced tumor volume (p<0.0001) and extended survival (p<0.0001). It yielded the highest human NK cell percentages among groups in blood at day 14 and, at endpoint, across blood, bone marrow, liver, lung, spleen, and tumor of treated mice. In serum, human IL-12 reached up to 34 pg/mL in 70CAR-12A3/18 or 70CAR-12A3 treated mice, while IL-18 averaged ∼1,300 pg/mL (70CAR-12A3/18) and ∼2,300 pg/mL (70CAR-18). No CRS-related cytokines were significantly elevated. Conclusion: We present a bidirectional TGFβ-sensing circuit that pairs constitutive IL-18 with TGFβ-inducible IL-12 for context-specific cytokine delivery and enhanced CAR NK activity. 70CAR-12A3/18 NK cells reduced tumor burden and extended survival in NSG mice bearing ccRCC xenografts without causing systemic toxicity. This modular TGFβ-sensor is generalizable, offering a blueprint for NK therapies targeting immunosuppressive TMEs in solid and hematologic tumors. Citation Format: Fuguo Liu, Xingyu Deng, Veronica W. Hui, Shikha Gupta, Wenxin Xu, Maily Nguyen, Mubin Tarannum, Andreia Maia, Shaobo Yang, Stephanie Sendker, Alaa K. Ali, John Koreth, Jose A. Cancellas, Jianzhu Chen, Robert Soiffer, Catherine Wu, Jerome Ritz, Toni K. Choueiri, Rizwan Romee. Engineering novel CAR NK cells to overcome TGF-β suppression in renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr A019.

Abstract Inside the cell nucleus, nuclear speckles are a predominant type of nuclear body present in the cells throughout our bodies. While first observed by Ramon y Cajal over 100 years ago, speckles have only recently been recognized as a major layer of gene regulation that boosts gene expression by assisting multiple steps of RNA production. Large genomic regions spanning 10s of megabases are consistently organized around speckles, with regulation of chromatin position at speckles occurring at finer scales of ∼10kb-1Mb. Hence, speckles may help direct functional programs within a cell by coordinating expression of large, but specific, groups of genes. In cancer, we found that speckles exist in two major states that correlate strongly with patient outcomes in neuroblastoma and clear cell renal cell carcinoma (ccRCC). These speckle states showed dramatic differences in expression of the speckle-associated gene neighborhoods. Because certain types of genes reside within speckle-associated chromatin, speckle states correlate with broad functional programs such as protein translation and oxidative phosphorylation as well as ccRCC-specific functional programs such as HIF-2alpha-induced angiogenesis and metabolism pathways. Consistent with distinct gene regulatory programs, ccRCC tumors display tumor microenvironment differences, particularly in tumor vasculature, between the two speckle states. While these data indicate that speckles can be used as a multifunctional readout for ccRCC tumor phenotypes, what drives speckle states in ccRCC is unclear. In other efforts in the lab, we combined analysis of public data with experimental approaches to uncover that transcription factors, hormone signaling, and immune signaling globally regulate expression of genes within speckle-associated chromatin. These efforts provide clues as to what may regulate nuclear speckle functions. Ultimately, by understanding the upstream drivers and downstream consequences of speckle states in ccRCC, we hope to advance nuclear speckles as potential therapeutic targets as well as biomarkers capable of stratifying patient risk and informing treatment decisions. Citation Format: Sana Mir, Hiroe Namba, Milena Stepic, Kate Alexander. Nuclear speckles in ccRCC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr IA025.

Abstract Introduction & Objectives The Von Hippel–Lindau (VHL) protein, frequently mutated in clear-cell renal cell carcinoma (ccRCC), is primarily recognized for its regulatory role over hypoxia-inducible factors (HIFs) and its ability to manage oxidative stress. However, less is known about its potential tumor-suppressive functions that are independent of the HIF pathway. This study focuses on its role in modulating autophagy in response to nutrient deprivation. Materials & Methods To investigate the HIF-independent role of VHL in ccRCC, we analyzed VHL-RCC samples and studied the molecular interactions between VHL and autophagy regulators under nutrient-deprived conditions. We identified a post-translational modification of ATG14, hydroxylation at Proline 54, facilitated by PHD1. The study then used mutant forms of ATG14(P54A) that cannot be hydroxylated to assess the importance of this modification for VHL's inhibition of autophagy. Results Our findings revealed that VHL plays a critical role in suppressing autophagy triggered by nutrient stress. In ccRCC samples lacking functional VHL, autophagic activity was significantly elevated, which was linked to worse patient outcomes, suggesting a correlation between increased autophagy and tumor progression. Mechanistically, we discovered that VHL binds to ATG14, but only after it undergoes hydroxylation at Pro54, a modification mediated by PHD1. This hydroxylation is crucial for preventing ATG14 from forming autophagy-initiating complexes with VPS34 and ATG14L. Mutations in ATG14 that prevent its hydroxylation (P54A) abolished VHL’s ability to inhibit autophagy, and tumors expressing this mutant form of ATG14showed reduced sensitivity to VHL's tumor-suppressing effects. Finally, the combination treatment in mouse models with VHL-deficient tumors, targeting both autophagy and HIF2α, led to a significant reduction in tumor growth. Conclusions This study uncovers a previously unknown HIF-independent mechanism by which VHL suppresses tumor growth through the regulation of autophagy. Our findings offer new insights into the role of VHL in ccRCC and suggest that therapies combining autophagy inhibitors and HIF2α inhibitors may offer a more effective treatment strategy for patients with VHL-deficient tumors. Citation Format: Chuandong Wang, Kan Gong. VHL inhibits autophagy and tumor development by modulating ATG14 hydroxylation in a PHD1-dependent manner [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr B010.

Understanding the composition of the tumor microenvironment is critical for cancer research. Spatial transcriptomics profiles gene expressions in spatial context, revealing tissue architecture and cellular heterogeneity, but its cost and technical complexity limit adoption. To address this issue, we introduce a pipeline to build STHELAR, a large-scale dataset that integrates spatial transcriptomics with Hematoxylin and Eosin (H&E) whole-slide images for cell type annotation. The dataset comprises 31 human Xenium FFPE sections across 16 tissue types, for 22 cancerous and 9 non-cancerous patients. It contains over 11 million unique biological cells, each assigned to one of ten curated cell-type categories designed to accommodate a pan-cancer setting. Annotations were derived through Tangram-based alignment to single-cell reference atlases, followed by slide-specific clustering and differential expression analysis. Co-registered H&E images enabled the extraction of over 500,000 patches with segmentation and classification masks. Quality control steps assessed segmentation accuracy, filtered out low-confidence regions, and verified annotation integrity. STHELAR provides a reference resource for developing models to predict cell-type annotations directly from histological images.

In Oregon, the incidence of Pancreatic Cancer is 2-times higher among American Indian and Alaska Native (AIAN) communities than among the rest of the population nationwide. We wanted to know if we could adapt the Research in Oregon Communities' Review System (ROCRS) to investigate this disparity while upholding tribal sovereignty. We partnered with The Confederated Tribes of Warm Springs with the goal of adapting the ROCR System to address the pancreatic cancer disparity with a culturally responsive approach. One-on-one interviews with community members were conducted at the annual Pi-Ume-Sha Health Fair in 2023. Cancer-related data were requested from the Northwest Portland Area Indian Health Board. Barriers to healthcare access were identified and categorized using PESTLE analysis. A Tribal liaison combined this analysis with cancer-related data to create a cultural landscape. This was done in accordance with ROCRS. This culturally responsive approach fosters trust and engagement in pancreatic cancer research and creates actionable insights for researchers while maintaining tribal sovereignty. The success of this model demonstrates the potential of tribally tailored research systems to improve participation and long-term collaborations with this underrepresented population.