Christine Sers's research while affiliated with Charité Universitätsmedizin Berlin and other places

Publications (24)

Article
3536 Background: We evaluated the prognostic and predictive impact of DNA mutations related to anti-EGFR antibody resistance in patients of the PANAMA trial, which compared Panitumumab (Pmab) and FU/FA versus FU/FA maintenance therapy after Pmab-FOLFOX induction therapy in RAS wild-type (wt) mCRC. Methods: Next generation panel sequencing was condu...
Article
Recurrence of tumor cells following local and systemic therapy is a significant hurdle in cancer. Most patients with metastatic colorectal cancer (mCRC) will relapse, despite resection of the metastatic lesions. A better understanding of the evolutionary history of recurrent lesions is required to identify the spatial and temporal patterns of metas...
Article
Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single‐cell studies have provided detailed insights into the cellula...
Preprint
BACKGROUND Recurrence of tumor cells following local and systemic therapy is a significant hurdle in cancer. Most patients with metastatic colorectal cancer (mCRC) will relapse, despite resection of the metastatic lesions. A better understanding of the evolutionary history of recurrent lesions is thus required to identify the spatial and temporal p...
Article
Full-text available
Background Pancreatic neuroendocrine neoplasms (PanNENs) fall into two subclasses: the well-differentiated, low- to high-grade pancreatic neuroendocrine tumors (PanNETs), and the poorly-differentiated, high-grade pancreatic neuroendocrine carcinomas (PanNECs). While recent studies suggest an endocrine descent of PanNETs, the origin of PanNECs remai...
Article
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Current treatment options for patients with advanced colorectal cancers (CRC) include anti-EGFR/HER1 therapy with the blocking antibody cetuximab. Although a subset of patients with KRAS wild-type disease initially respond to the treatment, resistance develops in almost all cases. Relapse has been associated with the production of the ligand heregu...
Article
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ECT2 is an activator of RHO GTPases that is essential for cytokinesis. Additionally, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in cancer patients. In this study, we observed e...
Article
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Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microe...
Preprint
Full-text available
Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread while no consensus treatment exists for metastasized carcinoids. Several recent sing...
Article
The COSMIC database (version 94) lists 576 genes in the Cancer Gene Census which have a defined function as drivers of malignancy (oncogenes) or as tumour suppressors (Tier 1). In addition, there are 147 genes with similar functions, but which are less well characterised (Tier 2). Furthermore, the overall number of genetic alterations found in tumo...
Article
Background Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are a rare and heterogeneous family of tumors arising from the disseminated neuroendocrine system of the gastrointestinal tract and pancreas. Clinical management of high-grade GEP-NEN is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facili...
Article
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Background: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predicti...
Article
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Cutaneous, ocular, and mucosal melanomas are histologically indistinguishable tumors that are driven by a different spectrum of genetic alterations. With current methods, identification of the site of origin of a melanoma metastasis is challenging. DNA methylation profiling has shown promise for the identification of the site of tumor origin in var...
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In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single-cell transcriptome analysis of tumors and matched non...
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Patient-derived xenograft (PDX) tumor models represent a valuable platform for identifying new biomarkers and novel targets, to evaluate therapy response and resistance mechanisms. This study aimed at establishment, characterization and therapy testing of colorectal carcinoma-derived PDX. We generated 49 PDX and validated identity between patient t...
Preprint
Full-text available
Recent developments in immuno-oncology demonstrate that not only cancer cells, but also features of the tumor microenvironment guide precision medicine. Still, the relationship between tumor and microenvironment remains poorly understood. To overcome this limitation and identify clinically relevant microenvironmental and cancer features, we applied...
Article
In colorectal cancer (CRC), the prevalence of NRAS mutations (5–9%) is inferior to that of KRAS mutations (40–50%). NRAS mutations feature lately during tumour progression and drive resistance to anti-EGFR therapy in KRAS wild-type tumours. To elucidate specific functions of NRAS mutations in CRC, we expressed doxycycline-inducible G12D and Q61K mu...
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An amendment to this paper has been published and can be accessed via the original article.
Article
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Background β-catenin activation plays a crucial role for tumourigenesis in the large intestine but except for Lynch syndrome (LS) associated cancers stabilizing mutations of β-catenin gene (CTNNB1) are rare in colorectal cancer (CRC). Previous animal studies provide an explanation for this observation. They showed that CTNNB1 mutations induced tran...
Article
Full-text available
Oncoproteins such as the BRAFV600E kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAFV600E-driven cytoplasmic signaling networks has proved ineffective, as patients regularly relapse with reactivation of the targeted pathways. We identify the nuclear protein SFPQ to be synthetically l...
Article
Full-text available
Background: Colorectal cancer (CRC) development is generally accepted as a sequential process, with genetic mutations determining phenotypic tumor progression. However, matching genetic profiles with histological transition requires the analyses of temporal samples from the same patient at key stages of progression. Results: Here, we compared th...
Article
Full-text available
To unravel vulnerabilities of KRAS-mutant CRC cells, a shRNA-based screen specifically inhibiting MAPK pathway components and targets was performed in CaCo2 cells harboring conditional oncogenic KRASG12V. The custom-designed shRNA library comprised 121 selected genes, which were previously identified to be strongly regulated in response to MEK inhi...
Article
Full-text available
We address whether combinations with a pan-RAF inhibitor (RAFi) would be effective in KRAS mutant pancreatic ductal adenocarcinoma (PDAC). Chemical library and CRISPR genetic screens identify combinations causing apoptotic anti-tumor activity. The most potent combination, concurrent inhibition of RAF (RAFi) and ERK (ERKi), is highly synergistic at...
Chapter
Transcriptomics is based on the fascinating capacity of analyzing simultaneously the entire set of RNA molecules or transcripts (messenger RNAs, microRNAs, long noncoding RNAs) produced in a population of cells or in tissues. While capturing transcript abundance on genome-wide level has become a routine task thanks to high-throughput technologies,...

Citations

... The best performing classifier combined the colorectal cancer dataset from Lee et al. [29] with the lung cancer from Laughney et al. [27], and achieved a minimal balanced accuracy of 0.97 on the validation data. The performance of the best performing gene set was tested on the hepatocellular carcinoma [32] (balanced accuracy of 0.93), and the lung carcinoid dataset [33] (balanced accuracy of 0.99). ...
... Some bsAbs are designed to bind EGFR and specific antigens on cytotoxic T lymphocytes (CTLs), e.g., CD28 (drug name: REGN7075, clinical trial: NCT04626635) or CD137 (drug name: BNA035; clinical trial: NCT05150457), and are expected to activate and redirect CTLs to target EGFR-expressing tumor cells, which may result in the CTL-mediated cell death of EGFR-expressing tumor cells [154,155]. The anticancer efficiency of several bifunctional proteins targeting EGFR and c-MET (MCLA-129, JNJ-61186372, and EMB-01) [146,147,150,[156][157][158][159]; HER3 (SI-B001) [160][161][162]; LGR5 (MCLA-158) [163,164]; TGFβ (BCA101) [165], MUC1 (M1231), CD28 (REGN7075), and CD137 (BNA035) are currently being tested in clinical studies. ...
... Recent large scale studies have been performed to define pNET genetic abnormalities (37)(38)(39)(40). Using whole exome sequencing of 10 nonfunctional, sporadic pNETs followed by directed sequencing of an additional 58 pNETs, Jiao, et al. confirmed the frequency of MEN1 mutations in 40% of cases, inactivation of TSC1/2 in 6% of cases and dysregulation of the P13K/mTOR signaling pathway by identifying PTEN inactivating mutations in 5% of cases. ...
... Initially, it seemed that cDC1 was the only DC subset involved in tumor immunity, however a more extensive analysis revealed the presence of other DC subsets [98] and the limited prevalence of cDC1 in human tumors [99]. Additionally, CD8+ T cells are not the only lymphocyte population involved in tumor immunity, and CD4+ T cells are known to be required in many tumor models [31,[100][101][102][103][104]. ...
... DNA methylation profiling shows a clear separation of pleomorphic sarcomas from nonmesenchymal neoplasms such as mesothelioma and melanoma, with the latter exhibiting distinct methylation signatures. 54,86,87 On the other hand, several tumor types, including undifferentiated pleomorphic sarcomas, myxofibrosarcomas, and many pleomorphic liposarcomas, are almost indistinguishable by their DNA methylation patterns. 45 Furthermore, sarcomas may exhibit a methylation profile differing from that of the respective reference set resulting in a failed prediction. ...
... Thus such finding can contribute to better treatment design [157]. Likewise, single cell analysis of normal colon and CRC tissue reveled WNT-independent MAPK activity in CRC as a key driver of tumor cell plasticity [158]. Furthermore, as CRC display a high degree of tumor heterogeneity, recent single-cell RNA sequencing analysis revealed heterogeneity in gene regulatory networks and identified CRC critical regulators such as transcription factor ERG [159]. ...
... Patient-derived xenograft (PDX) tumor models provide a valuable platform for identifying new biomarkers and novel targets, assessing treatment response, and resistance mechanisms [31]. To further explore the effects of miR-199a-3p and miR-199a-5p in vivo, we verified this with the PDX model using human fresh lung tumor tissue ( Figure 6A). ...
... Somatic CTNNB1 mutations have been previously associated with MLH1 germline variants, and a rather low prevalence of CTNNB1-mutant tumors among MLH1-associated incident cancers compared to their reported frequency in MLH1-associated prevalent cancers is unexpected and could point at different routes of progression between MLH1-associated incident and prevalent cancers. In addition, as somatic MLH1 and CTNNB1 mutations seem to be non-independent events [66], large deletions of the MLH1 gene prevailing in the Finnish population as a founder variant may have an impact on the routes of cancer progression and the likelihood of somatic CTNNB1 mutations [67]. The mechanistic reasons behind the association between MLH1 germline variants and CTNNB1 somatic mutations remain to be clarified by future studies. ...
... Mutations, which stabilize the CTNNB1 gene encoding for β-catenin and thus activate the canonical WNT/β-catenin signaling pathway, play a pivotal role in the pathogenesis of human [20,21] and canine [22] intestinal cancer. Based on previous immunohistochemical findings of other authors, showing that dysregulated and nuclear translocated β-catenin was present in spontaneous feline intestinal carcinomas [12], we shed light on the mutational status of feline CTNNB1 by performing Sanger sequencing of feline CTNNB1 exon 2 for the first time. ...
... SFPQ has both DNA and RNAbinding domains involved in a variety of cellular activities, including RNA transport, cell cycle regulation, DNA damage and repair, and apoptosis control. Several studies have reported that SFPQ can increase the growth, metastasis, and chemoresistance of cancer cells such as liver cancer, breast cancer, ovarian cancer, and colorectal cancers, although the precise mechanism by which SFPQ promotes cancer malignant phenotypes remains unknown (21)(22)(23)(24)(25)(26). ...