Novel Therapeutics in Soft Tissue Sarcoma.

There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma.

Not seeing the trees for the forest. The impact of neighbours on graph-based configurations in histopathology.

Background: Deep learning (DL) has set new standards in cancer diagnosis, significantly enhancing the accuracy of automated classification of whole slide images (WSIs) derived from biopsied tissue samples. To enable DL models to process these large images, WSIs are typically divided into thousands of smaller tiles, each containing 10-50 cells. Multiple Instance Learning (MIL) is a commonly used approach, where WSIs are treated as bags comprising numerous tiles (instances) and only bag-level labels are provided during training.

Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors.

Background: The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.

Methods: Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.

Efficacy of Combined PD-1 Inhibitor and Bevacizumab in Unresectable Liver Metastasis of MSI-H Colorectal Cancer: A Case Report.

BACKGROUND Programmed death 1 (PD-1) inhibitors have demonstrated limited effectiveness in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC). Recent studies suggest that their efficacy can be enhanced when combined with anti-angiogenic agents. CASE REPORT We present a case of a 25-year-old woman with CRC harboring a KRAS mutation and MSI-H status, along with initially unresectable liver metastases.

Bolus-Tracked Biphasic Contrast-Enhanced CT Imaging Following Microwave Liver Ablation Improves Ablation Zone Conspicuity and Semi-automatic Segmentation Quality.

Purpose: Contrast-enhanced CT (CECT) may be performed immediately following microwave liver ablation for assessment of ablative margins. However, practices and protocols vary among institutions. Here, we compare a standardized bolus-tracked biphasic CECT protocol and compare this with a single venous phase fixed delay protocol for ablation zone (AZ) assessment.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.

The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation.

Computational pathology applied to clinical colorectal cancer cohorts identifies immune and endothelial cell spatial patterns predictive of outcome.

Colorectal cancer (CRC) is a histologically heterogeneous disease with variable clinical outcome. The role the tumour microenvironment (TME) plays in determining tumour progression is complex and not fully understood. To improve our understanding, it is critical that the TME is studied systematically within clinically annotated patient cohorts with long-term follow-up.

NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.

Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer.

Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.

Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

A Single-Arm, Open-Label, Phase Ib Clinical Study Evaluating the Efficacy and Safety of Durvalumab in Combination with Albumin-Bound Paclitaxel and Carboplatin as Neoadjuvant Therapy for Resectable Stage III Non-Small Cell Lung Cancer.

Objective: This study aimed to explore the clinical efficacy and safety of durvalumab combined with albumin-bound paclitaxel and carboplatin as neoadjuvant therapy for resectable stage III Non-small Cell Lung Cancer (NSCLC).

Methods: A single-arm open-label phase Ib study was conducted. A total of 40 patients with driver gene-negative resectable stage III NSCLC were enrolled.

Dosimetry Software for Theranostic Applications: Current Capabilities and Future Prospects.

Dosimetry is integral to informed implementation of radiopharmaceutical therapies, enabling personalized treatment planning and ensuring patient safety by calculating absorbed doses to organs and tumors. As the therapeutic radiopharmaceutical field continues to expand, dosimetry software has emerged as a crucial tool for optimization of treatment efficacy. This review discusses key features and capabilities that current dosimetry software solutions have or should have in the future.

Causes and management of acute oncological pain: a narrative review.

Introduction: Acute pain in cancer is an important but often overlooked feature of many patients' oncological journey. Cancer-related pain is associated commonly with more persistent pain states caused by both the disease and its treatment, but there are numerous causes of acute pain which can develop in patients with cancer. This pain is frequently severe, can be challenging to manage and its suboptimal control can directly impact on oncological outcomes.

TCF12 and LncRNA MALAT1 Cooperatively Harness High Cyclin D1 but Low β-Catenin Gene Expression to Exacerbate Colorectal Cancer Prognosis Independently of Metastasis.

Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12-MALAT1 alliance is linked to poorer prognosis independently of age and metastasis.

Exploring PANoptosis in head and neck cancer: A novel approach to cancer therapy.

PANoptosis is a newly discovered complex programmed cell death (PCD) form. In the field of cancer research, PANoptosis is involved in multiple cell death pathways that affect tumor cell survival, proliferation, and response to treatment, serving as an innovative strategy for cancer therapy. Endocrine-disrupting chemicals (EDCs) impact the endocrine system, including cancer.

Investigating the added value of incorporatingmammographic density to an integrated breastcancer risk model with questionnaire-based riskfactors and polygenic risk score.

Introduction: Incorporation of mammographic density to breast cancer risk models could improve risk stratification to tailor screening and prevention strategies according to risk. Robust evaluation of the value of adding mammographic density to models with comprehensive information on questionnaire-based risk factors and polygenic risk score is needed to determine its effectiveness in improving risk stratification of such models.

Methods: We used the Individualized Coherent Absolute Risk Estimator (iCARE) tool for risk model building and validation to incorporate density to a previously validated literature-based model with questionnaire-based risk factors and a 313-variant polygenic risk score (PRS).

Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.

NLRP3 inflammasome-modulated angiogenic function of EPC via PI3K/ Akt/mTOR pathway in diabetic myocardial infarction.

Background: Inflammatory diseases impair the reparative properties of endothelial progenitor cells (EPC); however, the involvement of diabetes in EPC dysfunction associated with myocardial infarction (MI) remains unknown.

Methods: A model was established combining high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice with myocardial infarction. The therapeutic effects of transplanted wild-type EPC, Nlrp3 knockout EPC, and Nlrp3 overexpression EPC were evaluated.

Lenvatinib plus immunotherapy versus lenvatinib monotherapy in lenvatinib-insensitive patients with unresectable hepatocellular carcinoma: a retrospective study.

Purpose: The combination therapy of lenvatinib and immunotherapy as first-line treatment remains controversial in unresectable hepatocellular carcinoma (uHCC). This research aimed to compare the efficacy and safety of lenvatinib monotherapy (L) and combination therapy of lenvatinib and immune checkpoint inhibitor (LI) in lenvatinib-insensitive patients with uHCC.

Methods: Two hundred fifty-five uHCC patients were enrolled in this study.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.

FHIT is a fragile site tumor suppressor that is primarily inactivated upon tobacco smoking. FHIT loss is frequently observed in lung cancer, making it an important biomarker for the development of targeted therapy for lung cancer. Here, we report that inhibitors of glycogen synthase kinase 3 beta (GSK3β) and the homologous recombination DNA repair (HRR) pathway are synthetic lethal with FHIT loss in lung cancer.