Cancers

BackgroundWe previously established an ovarian carcinoma (OC) BRCA-like genomic copy number aberration profile classifier ("BRCA-like classifier"), which identifies tumors with deleterious mutations and epigenetic alterations in the homologous recombination pathway (1). We explored whether the classifier may also be predictive for therapies targeting tumors with homologous recombination deficiency (HRD) such as olaparib, a PARP inhibitor with synthetic lethal interaction with HRD, in combination...

BackgroundBevacizumab has been used in the first-line and recurrent treatment of ovarian cancer. However, the time-dependent changes in the effects of bevacizumab administration are not fully understood. MethodsThe ICON7-A cohort was generated from two ancillary analyses of the ICON7 trial. ICON7-A tumors were classified as homologous recombination deficient (HRD) or non-HRD based on their gene expression profiles. Kaplan-Meier curves from published phase III trials were graphically analyzed to...

BackgroundHigh ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection. Patients and methodsHome-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n=25, malignant n=29). All samples were tested for nine meth...

Human Papilloma virus (HPV)-mediated oropharyngeal cancer (OPC) has significantly better prognosis compared with HPV-negative, stimulating interest in treatment de-intensification approaches to reduce long-term sequelae. Routine clinical testing frequently utilises immunohistochemistry to detect upregulation of p16 protein as a surrogate marker of HPV-mediation. However, this does not detect discordant HPV+/p16-cases and incorrectly assigns HPV-/p16+ cases, which, given their inferior prognosis ...

High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumor microenvironment (TME) distinct from the primary tumors and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumor phenotype is essential for the development of effective new therapies. This study introduces a novel three-di...

BackgroundPlatinum chemotherapy is the cornerstone of treatment for high-grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum respo...

BackgroundChemoresistance is the key determinant of long-term survival in advanced high-grade serous ovarian cancer (HGSOC). The molecular mechanisms underlying chemoresistance in clinical populations are not clearly known. The study aimed to analyze the molecular mechanisms promoting chemoresistance, as well as neoadjuvant chemotherapy (NACT) induced sensitive-to-resistant transformation in advanced-HGSOC patients. MethodsRNA-sequencing data from Gene Expression Omnibus (GEO) database was syst...

BackgroundMorphology, clinical behavior, and genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. However, there is a substantial group of sporadic oncocytic tumors with peculiar hybrid phenotypes as well as a perplexing degree of morphologic and immunohistochemical overlap between classic RO and ChRCC with eosinophilic cytoplasm. The aim of this study is to provide detailed characterization of these hybrid tum...

BackgroundWhile platinum sensitivity and resistance have long been central to treatment decisions in high-grade serous ovarian cancer (HGSOC), these categories are increasingly questioned in real-world clinical settings. This study seeks to develop a prognostic model based on platinum-free interval (PFI) as a reliable indicator of patient prognosis, with additional exploration of chemotherapy resistance-related genes and pathways. Methods70 HGSOC patients with varied gene expression profiles an...

PurposeTriple-negative breast cancers (TNBC) account for 15% of all breast cancers but carry the worst prognosis. Because of their heterogenicity, these tumors are not all prone to targeted therapies. However, due to their high immune infiltration, targeting their immune microenvironment is of tremendous interest and is becoming the standard of care for high-risk early-stage TNBC. Nevertheless, the characterization of this immune infiltrate is often limited to general tumor-infiltrating lymphocy...

BackgroundWhile the prognostic value of immune-related biomarkers is well characterized in many solid tumors, their significance in vulva squamous cell carcinoma (VSCC) remains unclear. Here, we report a comprehensive analysis of programmed death-ligand 1 (PD-L1) and immune cell infiltrates in VSCC and establish immunoscore models for classification of the disease. MethodsArchival tissues, immunohistochemistry, and digital quantification were used to investigate the number of CD4+, CD8+, CD68+,...

Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The current approach for predicting the likelihood of response to ICB is a single proportional biomarker (PD-L1) expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with ...

Coloretcal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology ass...

PurposeThere remains an unmet need for preclinical models to enable personalized therapy for ovarian cancer (OC) patients. Recently, patient-derived organoid (PDO) cultures of patients with OC have been established that faithfully represent the histopathological features and genomic landscape of the patient tumor. In this study, we evaluate the capacity of OC PDOs to predict clinical drug response and functional consequences of tumor heterogeneity. Experimental design36 genomically characterize...

IntroductionFive to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA status. Material and methodsOut of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline BRCA pathogenic variant. We evaluated pre-NAC ...

Small intestinal neuroendocrine tumors (SI-NETs) are the most common tumor of the small intestine. Despite typically being metastatic at the time of diagnosis, the tumors are usually indolent and associated with a relatively long survival. Nevertheless, some patients fare worse and succumb to the disease soon after diagnosis despite similar stage and grade. To date, molecular prognostic markers are lacking, and our understanding of the disease biology is incomplete. Only CDKN1B is recurrently mu...

The mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using proteogenomic analysis of a panel of eight GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs. Notably, 5-fluorouracil (5FU) resistance was associated with PD-L1 expression, but not established GC subtypes. In publicly available cohort data, PD-L1 expression was associated with a reduced risk of GC progression. In addition to PD-L1, ...

Epithelial ovarian cancer (EOC) can be highly lethal, with limited therapeutic options for patients with non-homologous recombination deficient (HRD) disease. Folate receptor alpha (FOLR1/FR)-targeting agents have shown promise both alone and in combination with available therapies, but the relationship of FR to other treatment-driving biomarkers is unknown. The Cancer Genome Atlas (TCGA) was queried to assess protein and mRNA expression and mutational burden in patients with differential FR pro...

BackgroundAntibody-drug conjugates (ADCs) represent a promising therapeutic approach for high-grade serous ovarian carcinoma (HGSOC). Patient selection for ADC therapy depends on tumor target expression, making it essential to characterize molecular, spatial, and temporal heterogeneity. MethodsWe analyzed two HGSOC tissue microarray cohorts: 100 genomically profiled primaries (1,565 cores) and 64 matched cases with paired primary (P), primary disseminated (PD), and recurrent (R) samples (2,395 ...

PurposePathological complete response (pathCR) in rectal cancer, seen in examination of the pathological specimen post-surgery is the phenomenon whereby a tumour completely regresses under treatment with chemoradiotherapy. This is beneficial as up to 75% of patients do not experience regrowth of the primary tumour, allowing organ preservation and is poorly understood. We aimed to characterise the processes involved in pathCR. Materials & MethodsTwo groups of patients were identified with either...