ZMB Member Alexander Roesch
ZMB Member
Alexander Roesch
Next ZMB-Member
Prof. Dr. Alexander Roesch
Clinic for Dermatology
University Hospital Essen
Hufelandstraße 55
45147 Essen
- +49 201 723 4747
- Website
- Publications
-
- ZMB Research Program
Oncology
Research Overview
Melanoma is an aggressive tumor with dramatically reduced patient survival when disseminated to distant organs. Despite the historic success of modern cancer drugs, the cure of patients is hampered by the notorious tumor heterogeneity and plasticity of melanoma leading to therapy failure in most cases and limited diagnostic options to monitor therapy response/resistance over time.

© Alexander Roesch
Recent work and topics

© Alexander Roesch
Tumor cell state switching & Therapy resistance in melanoma
Accumulating evidence indicates that therapy and immune escape in cancer is not solely driven by genetic evolution, but also by the epigenetic adaptive plasticity of cell phenotypes. Current findings by us and others point to an understanding of melanoma as a highly plastic system, in which tumor cell subpopulations dynamically switch between multiple cellular identities (e.g. differentiated vs. de-differentiated, OXPHOS-driven vs. glycolytic, high vs. low ROS detoxifying, etc.) depending on the current therapeutic and microenvironmental context. As initiator and consortial member of the Clinical Research Unit CRU/KFO 337 (PhenoTImE), we are using established and patient-derived cell systems to study and track tumor cell states across different cancer entities in the context of signaling-targeted and immune checkpoint therapies. Technology-wise, our group applies for example cell state-directed fluorescent reporter constructs, multiplexed CODEX™ imaging, mass-spectrometry imaging, mass-spectrometric metabolomics, and, for cell manipulation, CRISPR/Cas9 editing and chemical compound libraries.
Dynamic therapy and immune escape. While the majority of cancer cells can be eliminated by first-line therapies and immune cell activation, a small portion of the tumor survives (minimal residual disease) and gives rise to clinical tumor relapse. The pre-resistant persister pool (DTP cells, dashed box) comprises a complex reservoir of different cell states from which repopulation of tumor heterogeneity dynamically emerges.
© Alexander Roesch
Regulation of tumor cell fate decisions
The phenotypic capacity to reversibly switch between different cell states provides a fundamental advantage for tumors to survive selective pressure. Our group has focused on the preclinical and clinical description of melanoma persister cell states over the past years. We have shown that melanomas irrespective of their genetic heterogeneity comprise multi-drug resistant, non-proliferating cells that repopulate the tumor and are identified by high expression of the histone H3K4 demethylase KDM5B (JARID1B). However, the exact role of KDM5B for regulating cellular identity and ways to exploit it for biomedical applications are still unclear; especially since the expression of KDM5B does not follow a static hierarchy, but is dynamically changing depending on the therapeutic con-text. Specifically, we hypothesize that KDM5B is a dynamic molecular switch that interconnects cell differentiation and cell cycle control. A deeper understanding of the switches between KDM5B levels and how this triggers transitions in cell states could lead to novel drugs with significant improvement in cancer treatment.
Dynamic cell fate decisions. Melanoma cells can dynamically shift between different differentiation, metabolic, and cell cycle states depending on the expression level of KDM5B/JARID1B.
© Alexander Roesch
Liquid biopsy and Tumor monitoring
Personalized oncology has not managed yet to overcome the limitation by inter- and intra-tumor heterogeneity in patients. This dilemma is even further complicated by the limited real-time information that translational research in humans but also in common mouse models can provide due to the high invasiveness of its mostly tissue biopsy-based design. In contrast, liquid biopsies, comprising the noninvasive analysis of circulating tumor-derived material in the blood, represent an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies; however, mostly unspecific markers are used for the sole assessment of tumor load so far, while biology-specific read-outs are not yet implemented. As part of the EU Horizon 2020 Marie Curie Training Program MELGEN and an active member of the European Liquid Biopsy Society (ELBS), we have established a multi-analyte, multi-marker liquid biopsy platform for diagnostic and therapy monitoring application. The goal of our LB projects is to develop a multilateral liquid biopsy platform that allows tumor load monitoring and assessment of tumor biological processes, such as phenotype switching, in melanoma patients and mouse models.
ctDNA-based serial monitoring for early prediction of therapy outcome. Serial monitoring of mutant ctDNA copies under therapy predicts clinical progression earlier as compared to routine radiologic scans
© Alexander Roesch
Publications
-
BAFF Attenuates Immunosuppressive Monocytes in the Melanoma Tumor MicroenvironmentIn: Cancer Research Vol. 82 (2022) Nr. 2, pp. 264 - 277
ISSN: 1538-7445; 0099-7374Online Full Text: dx.doi.org/ -
Checkpoint immunotherapy of cutaneous squamous cell carcinoma in patients suffering from chronic lymphocytic leukaemia : divergent outcomes in two men treated with PD-1 inhibitorsIn: Journal of the European Academy of Dermatology and Venereology Vol. 36 (2022) Nr. S1, pp. 41 - 44
ISSN: 0926-9959; 1468-3083Online Full Text: dx.doi.org/ (Open Access) -
Management of partial and non-responding cutaneous squamous cell carcinomaIn: Journal of the European Academy of Dermatology and Venereology Vol. 36 (2022) Nr. S1, pp. 29 - 34
ISSN: 0926-9959; 1468-3083Online Full Text: dx.doi.org/ (Open Access) -
Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition : Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 ImmunohistochemistryIn: Frontiers in Oncology Vol. 11 (2021)
ISSN: 2234-943XOnline Full Text: dx.doi.org/ (Open Access) -
Clinical characteristics and therapy response in unresectable melanoma patients stage IIIB-IIID with in-transit and satellite metastasesIn: European Journal of Cancer (EJC) Vol. 152 (2021) pp. 139 - 154
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ -
Coronavirus disease 2019 vaccine mimics lymph node metastases in patients undergoing skin cancer follow-up : A monocentre studyIn: European Journal of Cancer Vol. 154 (2021) pp. 167 - 174
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ (Open Access) -
Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic MelanomaIn: Frontiers in Oncology Vol. 11 (2021)
ISSN: 2234-943XOnline Full Text: dx.doi.org/ (Open Access) -
Factors influencing the adjuvant therapy decision : Results of a real-world multicenter data analysis of 904 melanoma patientsIn: Cancers Vol. 13 (2021) Nr. 10, pp. 2319
ISSN: 2072-6694Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Integrative genomic analyses of patient-matched intracranial and extracranial metastases reveal a novel brain-specific landscape of genetic variants in driver genes of malignant melanomaIn: Cancers Vol. 13 (2021) Nr. 4, pp. 731
ISSN: 2072-6694Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Leptomeningeal disease from melanoma : Poor prognosis despite new therapeutic modalitiesIn: European Journal of Cancer Vol. 148 (2021) pp. 395 - 404
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ -
Melanoma Differentiation Trajectories Determine Sensitivity Toward Pre-Existing CD8⁺ Tumor-Infiltrating LymphocytesIn: Journal of Investigative Dermatology Vol. 141 (2021) Nr. 10, pp. 2480 - 2489
ISSN: 1523-1747; 0022-202XOnline Full Text: dx.doi.org/ -
Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus TrametinibIn: Clinical Cancer Research Vol. 27 (2021) Nr. 16, pp. 4500 - 4510
ISSN: 1557-3265; 1078-0432Online Full Text: dx.doi.org/ (Open Access) -
The predictive and prognostic significance of cell-free DNA concentration in melanomaIn: Journal of the European Academy of Dermatology and Venereology Vol. 35 (2021) Nr. 2, pp. 387 - 395
ISSN: 1468-3083; 0926-9959Online Full Text: dx.doi.org/ (Open Access) -
Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED) : a randomised, double-blind, placebo-controlled, phase 2 trialIn: The Lancet Vol. 395 (2020) Nr. 10236, pp. 1558 - 1568
ISSN: 1474-547X; 0140-6736Online Full Text: dx.doi.org/ -
Drug-induced sarcoidosis-like reaction in adjuvant immunotherapy : Increased rate and mimicker of metastasisIn: European Journal of Cancer Vol. 131 (2020) pp. 18 - 26
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ -
Efficacy of cold atmospheric plasma vs. diclofenac 3% gel in patients with actinic keratoses : A prospective, randomized and rater-blinded study (ACTICAP)In: Journal of the European Academy of Dermatology and Venereology Vol. 34 (2020) Nr. 12, pp. E844 - E846
ISSN: 1468-3083; 0926-9959Online Full Text: dx.doi.org/ -
Fatal swelling of the groin – Clear cell sarcoma : A rare but important differential diagnosis to malignant melanomaIn: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 18 (2020) Nr. 10, pp. 1165 - 1168
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ (Open Access) -
Immuntherapie beim malignen MelanomIn: Der Internist Vol. 61 (2020) Nr. 7, pp. 669 - 675
ISSN: 1432-1289; 0020-9554Online Full Text: dx.doi.org/ (Open Access) -
Malignes Melanom : Stellenwert der BRAF-Inhibition beim malignen MelanomIn: Der Onkologe Vol. 26 (2020) Nr. 8, pp. 713 - 720
ISSN: 1433-0415; 0947-8965Online Full Text: dx.doi.org/ -
Plasma next generation sequencing and droplet digital-qpcr-based quantification of circulating cell-free rna for noninvasive early detection of cancerIn: Cancers Vol. 12 (2020) Nr. 2, pp. 353
ISSN: 2072-6694Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product FamilyIn: Chemistry: A European Journal Vol. 26 (2020) Nr. 39, pp. 8524 - 8531
ISSN: 1521-3765; 0947-6539Online Full Text: dx.doi.org/ (Open Access) -
Application of circulating cell-free tumor DNA profiles for therapeutic monitoring and outcome prediction in genetically heterogeneous metastatic melanomaIn: JCO Precision Oncology Vol. 3 (2019)
ISSN: 2473-4284Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Clinical and genetic analysis of melanomas arising in acral sitesIn: European Journal of Cancer Vol. 119 (2019) pp. 66 - 76
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ (Open Access) -
Metastatic Merkel cell carcinoma and myasthenia gravis : contraindication for therapy with immune checkpoint inhibitors?In: Journal for ImmunoTherapy of Cancer Vol. 7 (2019) Nr. 1, pp. 141
ISSN: 2051-1426Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Sequence-dependent cross-resistance of combined radiotherapy plus BRAFV⁶⁰⁰E inhibition in melanomaIn: European Journal of Cancer Vol. 109 (2019) pp. 137 - 153
ISSN: 1879-0852; 0959-8049Online Full Text: dx.doi.org/ -
Targeting the H3K4 Demethylase KDM5B Reprograms the Metabolome and Phenotype of Melanoma CellsIn: The Journal of Investigative Dermatology Vol. 139 (2019) Nr. 12, pp. 2506 - 2516.e10
ISSN: 1523-1747; 0022-202XOnline Full Text: dx.doi.org/ (Open Access) -
ctDNA as a noninvasive monitoring tool in metastatic melanomaIn: Journal of Clinical Oncology Vol. 37 (2019) Nr. Suppl. 15, pp. 9548
ISSN: 0732-183X; 1527-7755Online Full Text: dx.doi.org/ -
Actinic keratoses treated with cold atmospheric plasmaIn: Journal of the European Academy of Dermatology and Venereology Vol. 32 (2018) Nr. 1, pp. e37 - e39
ISSN: 0926-9959; 1468-3083Online Full Text: dx.doi.org/ -
MelanomaIn: The Lancet Vol. 392 (2018) Nr. 10151, pp. 971 - 984
ISSN: 0140-6736; 1474-547XOnline Full Text: dx.doi.org/ -
RNA-seq analysis identifies different transcriptomic types and developmental trajectories of primary melanomasIn: Oncogene Vol. 37 (2018) Nr. 47, pp. 6136 - 6151
ISSN: 0950-9232; 1476-5594Online Full Text: dx.doi.org/ -
Sebaceous tumours: more than skin deepIn: Gut Vol. 67 (2018) Nr. 11, pp. 2045 - 2053
ISSN: 0017-5749; 1468-3288Online Full Text: dx.doi.org/ -
A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of MelanomaIn: Cell Reports Vol. 21 (2017) Nr. 7, pp. 1953 - 1967
ISSN: 2211-1247Online Full Text: dx.doi.org/ (Open Access) -
Fulminant response to combined checkpoint inhibition with ipilimumab plus nivolumab after failure of nivolumab monotherapy in metastatic melanomaIn: European Journal of Cancer Vol. 83 (2017) pp. 142 - 145
ISSN: 0959-8049; 1879-2995Online Full Text: dx.doi.org/ -
Immunotherapy in melanoma : Recent advances and future directionsIn: European Journal of Surgical Oncology Vol. 43 (2017) Nr. 3, pp. 604 - 611
ISSN: 1532-2157; 0748-7983Online Full Text: dx.doi.org/ -
Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of klothoIn: Clinical Cancer Research Vol. 23 (2017) Nr. 12, pp. 3181 - 3190
ISSN: 1557-3265; 1078-0432Online Full Text: dx.doi.org/; Online Full Text: dx.doi.org/ (Open Access) -
Photoaging Mobile Apps as a Novel Opportunity for Melanoma Prevention: Pilot Study.In: JMIR mhealth and uhealth Vol. 5 (2017) Nr. 7,
ISSN: 2291-5222 -
Prognostic factors and treatment outcomes in 444 patients with mucosal melanomaIn: European Journal of Cancer Vol. 81 (2017) pp. 36 - 44
ISSN: 1879-2995; 0959-8049; 0014-2964; 1879-0852Online Full Text: dx.doi.org/ -
Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutationsIn: OncoTarget Vol. 8 (2017) Nr. 25, pp. 40683 - 40692
ISSN: 1949-2553Online Full Text: dx.doi.org/ (Open Access) -
Aetiology, comorbidities and cofactors of chronic leg ulcers : retrospective evaluation of 1 000 patients from 10 specialised dermatological wound care centers in GermanyIn: International Wound Journal Vol. 13 (2016) Nr. 5, pp. 821 - 828
ISSN: 1742-4801; 1742-481XOnline Full Text: dx.doi.org/ -
Arbeitsgemeinschaft Dermatologische Onkologie (ADO) : Bericht über den 3. ADO Nachwuchs-RetreatIn: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 14 (2016) Nr. 2, pp. 213 - 214
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ -
Checkpoint inhibitors in chronic kidney failure and an organ transplant recipientIn: European Journal of Cancer Vol. 67 (2016) pp. 66 - 72
ISSN: 0959-8049Online Full Text: dx.doi.org/ -
Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosisIn: Medicine Vol. 95 (2016) Nr. 29, pp. e4332
ISSN: 0025-7974Online Full Text: dx.doi.org/ (Open Access) -
JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral CancersIn: Cancer Research Vol. 76 (2016) Nr. 18, pp. 5538 - 5549
ISSN: 0008-5472; 1538-7445Online Full Text: dx.doi.org/ -
Medikamentöse Therapie des metastasierten malignen MelanomsIn: Arzneimitteltherapie Vol. 34 (2016) Nr. 1-2, pp. 14 - 22
ISSN: 0723-6913 -
Melanoma Lesions Independently Acquire T-cell Resistance during Metastatic LatencyIn: Cancer Research Vol. 76 (2016) Nr. 15, pp. 4347 - 4358
ISSN: 0008-5472; 1538-7445Online Full Text: dx.doi.org/ -
Patients with pyoderma gangrenosum - analyses of the German DRG data from 2012In: International Wound Journal Vol. 13 (2016) Nr. 5, pp. 951 - 956
ISSN: 1742-4801; 1742-481XOnline Full Text: dx.doi.org/ -
Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanomaIn: European Journal of Cancer Vol. 59 (2016) pp. 109 - 112
ISSN: 0959-8049Online Full Text: dx.doi.org/ -
Purpura fulminans related to paroxysmal nocturnal haemoglobinuriaIn: European Journal of Dermatology, EJD Vol. 26 (2016) Nr. 4, pp. 397 - 398
ISSN: 1167-1122Online Full Text: dx.doi.org/ -
The role of Orai–STIM calcium channels in melanocytes and melanomaIn: The Journal of Physiology Vol. 594 (2016) Nr. 11, pp. 2825 - 2835
ISSN: 1469-7793Online Full Text: dx.doi.org/ -
Combining BRAF(V) (600E) inhibition with modulators of the mitochondrial bioenergy metabolism to overcome drug resistance in metastatic melanomaIn: Experimental Dermatology Vol. 24 (2015) Nr. 9, pp. 709 - 710
ISSN: 1600-0625; 0906-6705Online Full Text: dx.doi.org/ -
Die multispektraloptoakustische Tomographie (MSOT) zur nichtinvasiven Diagnostik des Schildwächterlymphknotens bei Patienten mit malignem MelanomIn: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 13 (2015) Nr. 12, pp. 1323
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ -
MelanomaIn: Nature Reviews Disease Primers Vol. 1 (2015) pp. 15003
ISSN: 2056-676XOnline Full Text: dx.doi.org/ -
Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imagingIn: Immunotherapy Vol. 7 (2015) Nr. 317, pp. 317ra199
ISSN: 1750-7448; 1750-743XOnline Full Text: dx.doi.org/ -
Mitochondrial oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma cell subpopulationsIn: Experimental Dermatology Vol. 24 (2015) Nr. 2, pp. 155 - 157
ISSN: 1600-0625; 0906-6705Online Full Text: dx.doi.org/ Online Full Text (Open Access) -
Therapie des malignen MelanomsIn: Der Onkologe Vol. 21 (2015) Nr. 10, pp. 965 - 974
ISSN: 0947-8965Online Full Text: dx.doi.org/ -
Tumor heterogeneity and plasticity as elusive drivers for resistance to MAPK pathway inhibition in melanomaIn: Oncogene Vol. 34 (2015) Nr. 23, pp. 2951 - 2957
ISSN: 0950-9232; 1476-5594Online Full Text: dx.doi.org/ -
Tumorstammzellen im MelanomIn: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 13 (2015) Nr. 2, pp. 118 - 124
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ -
'TWIST and switch' metastasisIn: Pigment Cell and Melanoma Research Vol. 27 (2014) Nr. 2, pp. 157 - 158
ISSN: 1755-1471; 1755-148XOnline Full Text: dx.doi.org/ -
Arbeitsgemeinschaft Dermatologische Onkologie (ADO)In: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 12 (2014) Nr. 1, pp. 96 - 97
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ -
Bacterial spectrum colonizing chronic leg ulcers : a 10-year comparison from a German wound care centerIn: Journal der Deutschen Dermatologischen Gesellschaft (JDDG) Vol. 12 (2014) Nr. 12, pp. 1121 - 1127
ISSN: 1610-0387; 1563-2571; 1610-0379; 0301-0481Online Full Text: dx.doi.org/ -
Inverse regulation of melanoma growth and migration by Orai1/STIM2-dependent calcium entryIn: Pigment Cell and Melanoma Research Vol. 27 (2014) Nr. 3, pp. 442 - 453
ISSN: 1755-148XOnline Full Text: dx.doi.org/ -
SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathwayIn: The Journal of Investigative Dermatology Vol. 134 (2014) Nr. 4, pp. 1108 - 1118
ISSN: 0022-202X; 1523-1747Online Full Text: dx.doi.org/ -
Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases.In: Cancer Medicine Vol. 2 (2013) Nr. 1, pp. 76 - 85
ISSN: 2045-7634Online Full Text: dx.doi.org/ (Open Access)