Head-to-head study of [F]FAPI-04 PET/CT and [F]FDG PET/CT for non-invasive assessment of liver cancer and its immunohistochemical markers.

Objective: To compare the performance of [F]FDG and [F]FAPI-04 in PET/CT evaluation for liver cancer lesions, with a further exploration of the associations between PET semiquantitative data and immunohistochemical markers to liver cancer.

Methods: Patients with suspected malignant liver lesions (MLL) underwent [F]FDG and [F]FAPI-04 PET/CT scanning. Liver lesions were visually classified as positive or negative based on their uptake level exceeding that of adjacent normal liver tissue.

Germline sequencing in men with metastatic castration-resistant prostate cancer from the BARCODE2 study reveals a wide range of pathogenic variants in DNA repair genes.

Background: The presence of germline mutations plays an increasingly important role in risk assessment and treatment of prostate cancer (PrCa). Screening for high-risk mutations in subsets of patients is becoming routine. We explore the prevalence of germline genetic mutations in men with metastatic castration-resistant prostate cancer (mCRPC) recruited to the BARCODE2 trial.

Characterizing functional DNA damage and response caused by the combination of CHK1 and WEE1 inhibitors in ovarian and breast cancer models.

Background: We proposed to quantify reduction of functional DNA damage response (DDR) mechanisms caused by the combination of CHK1 and WEE1 inhibitors.

Methods: Survival of cells and tumor growth in-vitro and in-vivo caused by the combination of the CHK1 inhibitor SRA737 and the WEE1 inhibitor adavosertib was studied in OVCAR3 and MDA-MB 436 cells. Functional DNA damage was quantified using in vitro cell free DNA assays.

Incidental finding of leukaemia in circulating tumour DNA- the importance of a molecular tumour board.

As the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy.

Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer.

The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTX exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules.

The efficacy of combination immunotherapy with ipilimumab plus nivolumab in metastatic myxofibrosarcoma.

We present the case of a patient with Myxofibrosarcoma (MFS), a mesenchymal type of soft tissue sarcoma (STS) and the response to combination immunotherapy with anti PD-1 and anti-CTLA-4 therapy, following disease progression after Standard chemotherapy (SACT) and Radiotherapy (RT). We have shown a timeline of treatment and responses, as well as the overall safety profile and the management of immunotherapy related adverse events. This study demonstrates the potential of checkpoint inhibitors as therapeutic agents in the treatment of MFS.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults.

Background: Patients with PAX3/7-FOXO1 fusion-negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options.

Procedure: Histological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed.

Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection.

Background And Aims: Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection.

Discovery of 5-Nitro--(3-(trifluoromethyl)phenyl) Pyridin-2-amine as a Novel Pure Androgen Receptor Antagonist against Antiandrogen Resistance.

The transformation of clinical androgen receptor (AR) antagonists into agonists driven by AR mutations poses a significant challenge in treating prostate cancer (PCa). Novel anti-AR therapeutics combating mutation-induced resistance are required. Herein, by combining structure-based virtual screening and biological evaluation, a high-affinity agonist was first discovered.

Clinical, pathological, and computed tomography morphological features of lung cancer with spread through air spaces.

Background: Spread through air spaces (STAS) is significantly associated with decreased overall survival (OS) and reduced recurrence-free survival. However, there are no reliable methods to confirm the presence of STAS before surgery. The sensitivity and specificity of the intraoperative frozen section diagnosis of STAS are not satisfactory.

Life history dynamics of evolving tumors: insights into task specialization, trade-offs, and tumor heterogeneity.

The evolution of cancer cells parallels species evolution in numerous ways. Variations arise and spread under the pressure of competition between cancer cells. Current investigations of tumor evolution echo earlier debates between biologists.

Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer.

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.

Repeatability of quantitative MR fingerprinting for T and T measurements of metastatic bone in prostate cancer patients.

Objectives: MR fingerprinting (MRF) has the potential to quantify treatment response. This study evaluated the repeatability of MRF-derived T and T relaxation times in bone metastasis, bone, and muscle in patients with metastatic prostate cancer.

Materials And Methods: This prospective single-centre study included same-day repeated MRF acquisitions from 20 patients (August 2019-October 2020).

MGST1 facilitates novel KRAS inhibitor resistance in KRAS-mutated pancreatic ductal adenocarcinoma by inhibiting ferroptosis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a low 5-year survival rate. Treatment options for PDAC patients are limited. Recent studies have shown promising results with MRTX1133, a KRAS inhibitor that demonstrated potent antitumor activity in various types of tumors with KRAS mutation.

Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer.

CDK4/6 inhibition in combination with endocrine therapy is the standard of care for estrogen receptor (ER+) breast cancer, and although cytostasis is frequently observed, new treatment strategies that enhance efficacy are required. Here, we perform two independent genome-wide CRISPR screens to identify genetic determinants of CDK4/6 and endocrine therapy sensitivity. Genes involved in oxidative stress and ferroptosis modulate sensitivity, with GPX4 as the top sensitiser in both screens.

Electronic nicotine delivery system flavors, devices, and brands used by adults in the United States who smoke and formerly smoked in 2022: Findings from the United States International Tobacco Control Four Country Smoking and Vaping Survey.

Objective: This study estimated prevalence of current electronic nicotine delivery systems (ENDS) used by US adults who smoked cigarettes or formerly smoked in 2022 and assessed ENDS flavors, devices, and brands used most often.

Methods: Data are from the 2022 US ITC Smoking and Vaping Survey. Respondents were recruited from a web panel of a nationally representative sample of US adults ages 18+ who smoked, formerly smoked, and/or vaped ENDS.

Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity.

S100A9, a multifunctional protein mainly expressed by neutrophils and monocytes, poses an immunological paradox. In virus infections or sterile inflammation, it functions as an alarmin attracting innate immune cells, as well as mediating proinflammatory effects through TLR4 signaling. However, in cancer, S100A9 levels have been shown to associate with poor prognosis and lack of response to immunotherapy.

Tertiary lymphoid structure-associated B cells enhance CXCL13CD103CD8Trm cell response to PD-1 blockade in gastric cancer.

Background & Aims: Although the presence of tertiary lymphoid structures (TLS) correlates with positive responses to immunotherapy in many solid malignancies, the mechanism by which TLS enhances anti-tumor immunity is not well understood. The present study aimed to investigate the underlying cross-talk circuits between B cells and tissue-resident memory T (Trm) cells within the TLS and to understand their role in the context of immunotherapy.

Methods: Immunostaining and hematoxylin and eosin staining of TLS and CXCL13CD103CD8Trm cells were performed on tumor sections from patients with gastric cancer (GC).