Jens T Siveke

Jens T Siveke
University Hospital Essen | UK Essen · Bridge Institute of Experimental Tumor Therapy & DKTK Division of Solid Tumor Translational Oncology

Prof. Dr. med.

About

382
Publications
43,677
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
8,308
Citations
Citations since 2016
198 Research Items
5985 Citations
201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200
Introduction
Jens T Siveke currently heads the Division of Solid Tumor Translational Oncology (DKFZ/DKTK partner site Essen) and is senior physician in the Dep. of Medical Oncology at the West German Cancer Center, University Hospital Essen, Germany. Jens does translational research in GI Oncology.
Additional affiliations
January 2012 - present
Stony Brook University
January 2004 - December 2012
Technische Universität München
January 2004 - present
Klinikum der Universität München

Publications

Publications (382)
Article
Full-text available
Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. How...
Article
In the setting of ongoing SARS-CoV-2 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by 18F-FDG PET/CT. 68Ga-FAPI PET/CT is a new oncologic imaging tool that may overcome this limitation. Methods: We assessed post-vaccine, head-to-head and same-day 18F-FDG and 68Ga-FAPI-46 PET/CT...
Article
PURPOSE When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of...
Article
Background Positron emission tomography (PET) may differentiate responding and non-responding tumours early in the treatment of locally advanced gastroesophageal junction adenocarcinomas. Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods Patients underwent baseline ¹⁸F-FDG PET followed...
Article
Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly target tumor cells that can survive, adapt, and subclonally expand under primary therapy. Experimental design: To identify candidate markers and to experim...
Article
Full-text available
Background Existing risk scores appear insufficient to assess the individual survival risk of patients with advanced pancreatic ductal adenocarcinoma (PDAC) and do not take advantage of the variety of parameters that are collected during clinical care. Methods In this retrospective study, we built a random survival forest model from clinical data...
Article
Full-text available
Biliary-tract-carcinomas (BTC), pancreatic-ductal-adenocarcinomas (PDAC) and adenoidcystic-carcinomas (AC) have in common that they are traditionally treated with large clinical-target-volumes (CTV). The aim of this study is to examine the impact of pretreatment-[⁶⁸Ga]FAPI-PET/CT on target-volume-definition and posttreatment-[⁶⁸Ga]FAPI-PET/CT-respo...
Article
Full-text available
Purpose Pancreatic ductal adenocarcinoma (PDAC) is a molecularly heterogeneous tumor entity with no clinically established imaging biomarkers. We hypothesize that tumor morphology and physiology, including vascularity and perfusion, show variations that can be detected by differences in contrast agent (CA) accumulation measured non-invasively. This...
Article
Full-text available
Purpose High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) are rare and heterogeneous malignancies with poor prognosis. Aim of this study was to develop prognosticators identifying those patients that derive the most benefit from currently available systemic therapies. Methods This retrospective analysis included 78 patients w...
Article
Background The multi-receptor tyrosine kinase inhibitor pazopanib is approved for the treatment of advanced soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to select patients who are likely to benefit from this drug. Patients and methods...
Article
Full-text available
Purpose When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of...
Article
Full-text available
Objective Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and ta...
Article
Full-text available
Pancreatoblastoma (PB) is a rare tumor of the pancreas. In case of metastases, the treatment options are sparse and targeted approaches are not developed. We here evaluate MCL1 amplification as a putative target in PB. Thirteen samples from adult (10/13) and pediatric patients (3/13) were collected. Three of these samples had been previously subjec...
Article
Full-text available
Background The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs). Patients and methods A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [I...
Article
Full-text available
Background Germline variant evaluation in precision oncology opens new paths towards the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly ra...
Article
Purpose: We report efficacy and safety of 90Y-FAPI-46-RLT in patients with advanced sarcoma, pancreatic cancer (PDAC) and other cancer entities. Experimental design: Up to four cycles of RLT were offered to patients with (a) progressive metastatic malignancy, (b) exhaustion of approved therapies, and (c) high fibroblast activation protein (FAP)...
Preprint
Background: Pancreatic Ductal Adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichm...
Preprint
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. Drug resistance is the major cause for therapeutic failure in PDAC patients with progressive disease. The mechanisms underlying resistance formation are complex and remain poorly understood. To gain insights into molecular changes during the formation of resistance...
Article
Importance: Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures. Objective: To develop a consensus on baseline...
Article
Full-text available
Purpose In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investi...
Article
Full-text available
Background Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup. Patients and methods Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter s...
Article
Background: The incidence of pancreatic cancer (PC) is increasing. Due to a combination of therapeutic resistance and to advanced disease already at diagnosis, PC remains one of the most fatal malignant solid tumors with a 5-year survival rate of only 8–9%.Objectives: The German oncology study groups offer a broad portfolio of clinical trials. We p...
Article
Full-text available
Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall surviva...
Article
Full-text available
Background Radiology is the current standard for monitoring treatment responses in lung cancer. Limited sensitivity, exposure to ionizing radiations and related sequelae constitute some of its major limitation. Non-invasive and highly sensitive methods for early detection of treatment failures and resistance-associated disease progression would hav...
Article
Full-text available
Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments diffe...
Article
VEGF inhibition in gastric cancer has a proven benefit in the second line setting [1–3]. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, −2 and − 3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluoro...
Article
Full-text available
Statins are among the most commonly prescribed drugs, and around every fourth person above the age of 40 is on statin medication. Therefore, it is of utmost clinical importance to understand the effect of statins on cancer cell plasticity and its consequences to not only patients with cancer but also patients who are on statins. Here, we find that...
Article
Full-text available
Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inh...
Article
Full-text available
Background: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. Methods: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRF...
Article
Full-text available
The protein kinase Akt plays a pivotal role in cellular processes. However, its isoforms’ distinct functions have not been resolved to date, mainly due to the lack of suitable biochemical and cellular tools. Against this background, we present the development of an isoform-dependent Ba/F3 model system to translate biochemical results on isoform spe...
Article
Full-text available
The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed f...
Article
Full-text available
Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could pote...
Article
Introduction: Fibroblast activation protein (FAP) is overexpressed in several solid tumors and therefore represents an attractive target for radiotheranostic applications. Recent investigations demonstrated rapid and high uptake of small-molecule inhibitors of FAP (68Ga-FAPI-46) for PET imaging. Here, we report our initial experience in terms of fe...
Preprint
Full-text available
Pancreatic Ductal Adenocarcinoma (PDAC) lacks targeted treatment options. Although subtypes with transcriptome-based distinct lineage and differentiation features have been identified, deduced clinically actionable targets remain elusive. We here investigate functional metabolic features of the classical and QM (quasi-mesenchymal)/basal-like PDAC s...
Article
Full-text available
Background The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular d...
Article
Ampullary carcinoma is a rare malignant neoplasm and arises in the region of Vater's ampulla. The differentiation from pancreatic and distal cholangiocarcinoma can be difficult. The prognosis is more favorable than for pancreatic ductal adenocarcinoma but recurrences are frequent. An exact diagnostic clarification and differentiation from pancreati...
Article
Full-text available
Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor c...
Article
Full-text available
The use of MEK inhibitors in the therapy of uveal melanoma (UM) has been investigated widely but has failed to show benefits in clinical trials due to fast acquisition of resistance. In this study, we investigated a variety of therapeutic compounds in primary-derived uveal melanoma cell lines and found monosomy of chromosome 3 (M3) and mutations in...
Article
The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults...
Article
3566 Background: Patients (pts) with mCRC progressing on standard chemotherapy have limited therapeutic options. Trifluridine/tipiracil (TAS102) significantly improved survival in patients with refractory mCRC. Ramucirumab (ram) is approved in combination with FOLFIRI for second-line treatment. There is a strong rationale to evaluate the efficacy a...
Article
Full-text available
Background The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. Patients and methods 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1–11) treatme...
Article
Full-text available
Synonymous mutations are generally disregarded by genomic analyses because they are considered non-pathogenic. We identified and characterized a somatic synonymous mutation in the epigenetic modifier and tumor suppressor BAP1, resulting in exon skipping and complete protein inactivation. This radically altered the prognosis of a clear-cell renal ce...
Article
Full-text available
Objective: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. Methods: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG scor...
Preprint
Full-text available
Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain elusive. Here, we unveiled a cancer cell-autonomous function of PGRN in driving immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN was associated with poor overall survival i...
Chapter
Well-defined outcome measures enable comparisons between clinical trials. However, the reporting of baseline and prognostic characteristics largely vary in studies investigating potentially resectable pancreatic cancer patients. This makes accurate comparisons between studies challenging. By standardization of the reporting of mandatory baseline an...