Molecular Oncology

Paired related homeobox 1 (PRRX1) is an inducer of epithelial-to-mesenchymal transition (EMT) in different types of cancer cells. We detected low PRRX1 expression in nevus but increased levels in primary human melanoma and cell lines carrying the BRAFV600E mutation. High expression of PRRX1 correlates with invasiveness and enrichment of genes belonging to the EMT programme. Conversely, we found that loss of PRRX1 in metastatic samples is an independent prognostic predictor of poor survival for melanoma patients...

M. Lagadari, N. R. Zgajnar, L. I. Gallo and M. D. Galigniana, 'Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity', Molecular Oncology 10, no. 7 (2016): 1086-1098, https://doi.org/10.1016/j.molonc.2016.05.002. The above article, published online on 17 May 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Kevin Ryan and John Wiley and Sons Ltd. The retraction has been agreed due to several instances of image manipulation in figures 1C, 5B, 4A and 5A...

The reliance on mortality endpoints in cancer screening trials is not always compatible with the need to accelerate progress in outcomes for patient and public benefit. Evaluation of novel cancer screening technologies, such as multi-cancer early detection (MCED) tests, could be expedited by using alternative metrics that are measurable earlier than mortality. These include endpoints based on cancer stage at diagnosis, such as reduction in late-stage cancer incidence, and endpoints following cancer diagnosis, such as eligibility for curative therapy...

We have previously identified increased levels of distinct bacterial taxa within mucosal biopsies from colorectal cancer (CRC) patients. Following prior research, the aim of this study was to investigate the detection of the same CRC-associated bacteria in fecal samples and to evaluate the suitability of fecal samples as a non-invasive material for the detection of CRC-associated bacteria. Next-generation sequencing (NGS) of the 16S ribosomal RNA (rRNA) V4 region was performed to evaluate the detection of the CRC-associated bacteria in the fecal microbiota of cancer patients, patients with adenomatous polyp and healthy controls...

The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5) is emerging as a promising target in cancer. Indeed, alterations of the MEK5/ERK5 pathway are present in many types of cancer, including melanoma. One of the key events in MAPK signalling is MAPK nuclear translocation and its subsequent regulation of gene expression. Likewise, the effects of ERK5 in supporting cancer cell proliferation have been linked to its nuclear localization. Despite many processes regulating ERK5 nuclear translocation having been determined, the nuclear transporters involved have not yet been identified...

MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC's function from being a gene-specific transcription factor to an essential stress resilience factor...

Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy. Specific tumor biomarkers, such as delta-like ligand 3 (DLL3) and schlafen11 (SLFN11), may enable the selection of more efficacious, novel immunomodulating targeted treatments like bispecific T-cell engaging monoclonal antibodies (tarlatamab) and chemotherapy with PARP inhibitors. However, obtaining a tissue biopsy sample can be challenging in SCLC...

Retraction: C. Jin, J. Zhao, Z-P. Zhang, M. Wu, J. Li, B. Liu, X-B. Liao, Y-X. Liao, and J-P. Liu, "CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10," Molecular Oncology 15, no. 2 (2020): 596-622, https://doi.org/10.1002/1878-0261.12830. The above article, version of record published online on 16 December 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan; FEBS Press; and John Wiley & Sons Ltd...

K. Liu, J.-D. Ni, W.-Z. Li, B.-Q. Pan, Y.-T. Yang, Q. Xia and J. Huang, "The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-Catenin Cascade Promotes Malignant and Metastatic Progression of Osteosarcoma," Molecular Oncology 14, no. 10 (2020): 2678-2695, https://doi.org/10.1002/1878-0261.12760. The above article, version of record published online on 29 August 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Kevin Ryan and John Wiley and Sons Ltd...

Immune checkpoint blockade has emerged as a potent new tool in the war on cancer. However, only a subset of cancer patients benefit from this therapeutic modality, sparking a search for combination therapies to increase the fraction of responding patients. We argue here that inhibition of protein phosphatase 2A (PP2A) is a promising approach to increase responses to immune checkpoint blockade and other therapies that rely on the presence of tumor-reactive T cells. Inhibition of PP2A increases neoantigen expression on tumor cells, activates the cGAS/STING pathway, suppresses regulatory T cells, and increases cytotoxic T cell activation...

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin-fixed paraffin-embedded (FFPE) samples for analysis at the DNA level using panel-based next-generation sequencing and array-comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray...

Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in the treatment of relapsed/refractory melanoma and hematological malignancies, respectively. These treatments have marked a pivotal shift in cancer management. However, as "living drugs," their effectiveness is dependent on their ability to proliferate and persist in patients. Recent studies indicate that the mechanisms regulating these crucial functions, as well as the T cell's differentiation state, are conditioned by metabolic shifts and the distinct utilization of metabolic pathways...

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell-tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label-retaining slow-cycling leukemia cell population from AML1-ETO9a (AE9a) leukemic mice. We find that, compared with cells not maintaining PKH-staining, a higher proportion of PKH-retaining cells are in G0 phase, and PKH-retaining cells exhibit increased colony formation ability and leukemia initiation potential...

Low-grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma...

The concept of precision oncology, the application of targeted drugs based on comprehensive molecular profiling, has revolutionized treatment strategies in oncology. This review summarizes the current status of precision oncology in glioblastoma (GBM), the most common and aggressive primary brain tumor in adults with a median survival below 2 years. Targeted treatments without prior target verification have consistently failed. Patients with BRAF V600E-mutated GBM benefit from BRAF/MEK-inhibition, whereas targeting EGFR alterations was unsuccessful due to poor tumor penetration, tumor cell heterogeneity, and pathway redundancies...

Liquid biopsy demonstrates excellent potential in patient management by providing a minimally invasive and cost-effective approach to detecting and monitoring cancer, even at its early stages. Due to the complexity of liquid biopsy data, machine-learning techniques are increasingly gaining attention in sample analysis, especially for multidimensional data such as RNA expression profiles. Yet, there is no agreement in the community on which methods are the most effective or how to process the data. To circumvent this, we performed a large-scale study using various machine-learning techniques...

Interferon regulatory factor 4 (IRF4) was initially identified as a key controller in lymphocyte differentiation and function, and subsequently as a dependency factor and therapy target in lymphocyte-derived cancers. In melanocytes, IRF4 takes part in pigmentation. Although genetic studies have implicated IRF4 in melanoma, how IRF4 functions in melanoma cells has remained largely elusive. Here, we confirmed prevalent IRF4 expression in melanoma and showed that high expression is linked to dependency in cells and mortality in patients...

A first-in-human trial demonstrated that a vaccine targeting the histone mutation H3K27M can induce an immune response, in a mutation-specific manner, in patients with diffuse midline glioma. In a recent study by Boschert et al., the same group now dissects the functional immune response triggered after effective vaccination of one of the patients, who has been in remission for over 3 years. The H3K27M peptide vaccine, named H3-vac, induces a CD4+ T-cell-specific immune response in this patient and expands the repertoire of polyclonal H3K27M-specific T-cell receptors...

Gemcitabine plus cisplatin (GC) combination chemotherapy is the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, most cases develop resistance to this therapy. We investigated whether drug resistance could be targeted through metabolic reprogramming therapies. Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells...

Hepatocellular carcinoma is one of the deadliest and fastest-growing cancers. Among HCC etiologies, metabolic dysfunction-associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD-driven HCC development...