Molecular Oncology

Currently, the knowledge of long non-coding RNA (lncRNA)-encoded peptides is quite lacking in esophageal squamous cell carcinoma (ESCC). In this study, we simultaneously identified six lncRNA open reading frames (ORFs) with peptide-coding abilities including lysine-specific demethylase 4A antisense RNA 1 (KDM4A-AS1) ORF by combining weighted gene co-expression network analysis (WGCNA) for ESCC clinical samples, ribosome footprints, ORF prediction, mass spectrometry (MS) identification, and western blotting...

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (ECBP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research...

No abstract text is available yet for this article.

Extracellular vesicles (EVs) are an important regulatory factor for natural killer cell activity (NKA) in the tumor microenvironment. The relationship between circulating EVs in the peripheral blood and natural killer (NK) cells in prostate cancer is unclear. This study aims to investigate the key regulators in the interaction between circulating EVs and NK cells in prostate cancer patients before and after tumor removal. NK-cell characteristics were prospectively assessed in 79 patients treated with robot-assisted laparoscopic radical prostatectomy (RARP) preoperatively and postoperatively...

LIM protein-domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein-protein interactions, signaling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues compared with normal tissues, but its specific molecular function in CRC progression is still not very clear. Here, we found that, in CRC cancer cell lines, overexpression of AJUBA decreased p53 levels, whereas knockdown of AJUBA significantly increased p53 levels...

Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and non-coding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To address the problem, we propose the following recommendations: 1) accurate documentation of experimental procedures in Materials and Methods (and not only in the supplementary information, as many journals have a strict mandate for making Materials and Methods as visible as possible in the main text); 2) submission of RT-qPCR raw data for all experiments reported; and 3) adoption of a unified, simple format for submitted RT-qPCR raw data...

Human epidermal growth factor receptor 2 (ErbB2/HER2) is a tyrosine kinase receptor that is overexpressed in 25% of primary human breast cancers, as well as in multiple other cancers. HER2-targeted therapies improved progression-free and overall survival in patients with HER2+ breast cancers. However, associated resistance mechanisms and toxicity highlight the need for new therapeutic approaches for these cancers. We recently established that, in normal cells, HER2 is stabilized in a catalytically repressed state by a direct interaction with members of the ezrin/radixin/moesin (ERM) family...

Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumors have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower mean survival months...

Treatment with immune checkpoint inhibitors (ICI) has revolutionized cancer management for multiple tumor types, including breast cancer. However, not all patients respond to ICI and unraveling the determinants and mechanisms of response still remains an unmet need. A recent study has uncovered the critical role of eosinophils in mediating immunotherapy effect in breast cancer, mainly by stimulating the activation of CD8+ T-cells. Furthermore, the intratumoral eosinophil recruitment was directed by CD4+ T-cells and the interleukins IL-5 and IL-33, thus providing the rationale for targeting eosinophils to enhance ICI response...

Taselisib is a potent β-sparing phosphatidylinositol 3-kinase (PI3K) inhibitor that, with endocrine therapy, improves outcomes in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAmut) advanced breast cancer. To understand alterations associated with response to PI3K inhibition, we analyzed circulating tumor DNA (ctDNA) from participants enrolled in the SANDPIPER trial. Participants were designated as either PIK3CAmut or PIK3CA no mutation detected (NMD) per baseline ctDNA...

Alternative sources of tumor information need to be explored in patients with non-small cell lung cancer (NSCLC). Here, we compared programmed cell death 1 ligand 1 (PD-L1) expression on cytology imprints and circulating tumor cells (CTCs) with PD-L1 tumor proportion score (TPS) from immunohistochemistry staining of tumor tissue from patients with NSCLC. We evaluated PD-L1 expression using a PD-L1 antibody (28-8) in representative cytology imprints, and tissue samples from the same tumor. We report agreement rates on PD-L1 positivity (TPS ≥ 1%) and high PD-L1 expression (TPS ≥ 50%)...

In colorectal cancer, the mechanisms underlying tumor aggressiveness require further elucidation. Taking advantage of a large panel of human metastatic colorectal cancer xenografts and matched stem-like cell cultures (m-colospheres), here we show that overexpression of microRNA 483-3p (miRNA-483-3p; also known as MIR-483-3p), encoded by a frequently amplified gene locus, confers an aggressive phenotype. In m-colospheres, endogenous or ectopic miRNA-483-3p overexpression increased proliferative response, invasiveness, stem-cell frequency and resistance to differentiation...

Control of tumor development and growth by the immune system critically defines patient fate and survival. What regulates the escape of colorectal tumors from destruction by the immune system is currently unclear. Here, we investigated the role of intestinal synthesis of glucocorticoids in the tumor development during inflammation-induced mouse model of colorectal cancer. We demonstrate that the local synthesis of immunoregulatory glucocorticoids has dual roles in the regulation of intestinal inflammation and tumor development...

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5-year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced-stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high-quality ovarian-tissue-specific spectral library containing 130,735 peptides and 10,696 proteins on Orbitrap instruments...

As homologous recombination deficiency (HRD) is a biomarker to predict the efficiency of PARP inhibitor treatment, this study developed a non-exonic single-nucleotide polymorphism (SNP)-based targeted next-generation sequencing (Tg-NGS) panel and comprehensively examined it both on standards and clinical ovarian cancer tissues. The HRD scores calculated by the panel and whole-genome sequencing (WGS) were consistent, and the analysis by Sequenza was the most reliable. The results on clinical samples revealed that the panel performed better in HRD analysis than SNP microarray...

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICIs benefit. We applied sWGS on cell-free DNA (cfDNA) extracted from plasma samples of 45 patients with metastatic NSCLC treated with ICIs...

Triple negative breast cancers (TNBCs) represent 15-20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo-adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers of AC response in patient-derived xenograft (PDX) models of TNBC and to validate them in the clinical setting. By gene and protein expression analysis of 39 PDX with different responses to AC, we found that high expression of HORMAD1 was associated with better response to AC...

Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. We performed high-depth whole-exome sequencing (200x) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples and 18 normal tissue samples...

The role of long non-protein-coding RNAs (lncRNAs) in p53-mediated tumor suppression has become increasingly appreciated in the past decade. Thus, the identification of p53-regulated lncRNAs can be a promising starting point to select and prioritize lncRNAs for functional analyses. By integrating transcriptome and transcription factor binding data, we identified 379 lncRNAs that are recurrently differentially regulated by p53. Dissecting the mechanisms by which p53 regulates many of them, we identified sets of lncRNAs regulated either directly by p53 or indirectly through the p53-RFX7 and p53-p21-DREAM/RB:E2F pathways...

Targeted therapies have become a mainstay in the treatment of cancer, but their long-term efficacy is compromised by acquired drug resistance. Acquired therapy resistance develops via two phases - first through adaptive development of non-genetic drug tolerance which is followed by stable resistance through acquisition of genetic mutations. Drug tolerance has been described in practically all clinical cancer treatment contexts, and detectable drug-tolerant tumors are highly associated with treatment relapse and poor survival...