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Article ; Online: Enhancing personalized immune checkpoint therapy by immune archetyping and pharmacological targeting.

Cerella, Claudia / Dicato, Mario / Diederich, Marc

2023 Volume 196, Page(s) 106914

Abstract: Immune checkpoint inhibitors (ICIs) are an expanding class of immunotherapeutic agents with the potential to cure cancer. Despite the outstanding clinical response in patient subsets, most individuals become refractory or develop resistance. Patient ... ...

Abstract	Immune checkpoint inhibitors (ICIs) are an expanding class of immunotherapeutic agents with the potential to cure cancer. Despite the outstanding clinical response in patient subsets, most individuals become refractory or develop resistance. Patient stratification and personalized immunotherapies are limited by the absence of predictive response markers. Recent findings show that dominant patterns of immune cell composition, T-cell status and heterogeneity, and spatiotemporal distribution of immune cells within the tumor microenvironment (TME) are becoming essential determinants of prognosis and therapeutic response. In this context, ICIs also function as investigational tools and proof of concept, allowing the validation of the identified mechanisms. After reviewing the current state of ICIs, this article will explore new comprehensive predictive markers for ICIs based on recent discoveries. We will discuss the recent establishment of a classification of TMEs into immune archetypes as a tool for personalized immune profiling, allowing patient stratification before ICI treatment. We will discuss the developing comprehension of T-cell diversity and its role in shaping the immune profile of patients. We describe the potential of strategies that score the mutual spatiotemporal modulation between T-cells and other cellular components of the TME. Additionally, we will provide an overview of a range of synthetic and naturally occurring or derived small molecules. We will compare compounds that were recently identified by in silico prediction to wet lab-validated drug candidates with the potential to function as ICIs and/or modulators of the cellular components of the TME.
Language	English
Publishing date	2023-09-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2023.106914
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Zs.A 721: Show issues

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Article: Editorial: Next-Generation Cancer Therapies Based on a (R)evolution of the Biomarker Landscape.

Cerella, Claudia / Lorant, Anne / Aquilano, Katia / Diederich, Marc

Frontiers in pharmacology

2022 Volume 13, Page(s) 861424

Language	English
Publishing date	2022-03-07
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.861424
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Book ; Online: Chapter Naturally Occurring Organic Sulfur Compounds: An Example of a Multitasking Class of Phytochemicals in Anti-Cancer Research

Dicato, Mario / Viry, Elodie / Diederich, Marc / Cerella, Claudia / Kelkel, Mareike / Jacob, Claus

2011

Keywords	Renal medicine & nephrology ; Medicine
Size	1 Online-Ressource
Publisher	InTechOpen
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021047956
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: BH3 Mimetics in AML Therapy: Death and Beyond?

Cerella, Claudia / Dicato, Mario / Diederich, Marc

Trends in pharmacological sciences

2020 Volume 41, Issue 11, Page(s) 793–814

Abstract: B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics are targeted therapeutic agents that allow response prediction and patient stratification. BH3 mimetics are prototypical activators of the mitochondrial death program in cancer. They emerged as ... ...

Abstract	B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics are targeted therapeutic agents that allow response prediction and patient stratification. BH3 mimetics are prototypical activators of the mitochondrial death program in cancer. They emerged as important modulators of cellular mechanisms contributing to poor therapeutic responses, including cancer cell stemness, cancer-specific metabolic routes, paracrine signaling to the tumor microenvironment, and immune modulation. We present an overview of the antagonism between BH3 mimetics and antiapoptotic BCL2 proteins. We focus on acute myeloid leukemia (AML), a cancer with reduced therapeutic options that have recently been improved by BH3 mimetics.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Biomimetic Materials/pharmacology ; Clinical Trials, Phase I as Topic ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Protein Domains ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Antineoplastic Agents ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2020-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2020.09.004
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Zs.A 1513: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 6: Show issues

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Article ; Online: Non-canonical programmed cell death mechanisms triggered by natural compounds.

Diederich, Marc / Cerella, Claudia

Seminars in cancer biology

2016 Volume 40-41, Page(s) 4–34

Abstract: Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural ... ...

Abstract	Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction.
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2016.06.001
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Zs.A 2922: Show issues

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Article ; Online: Natural scaffolds in anticancer therapy and precision medicine.

Mazumder, Aloran / Cerella, Claudia / Diederich, Marc

Biotechnology advances

2018 Volume 36, Issue 6, Page(s) 1563–1585

Abstract: The diversity of natural compounds is essential for their mechanism of action. The source, structures and structure activity relationship of natural compounds contributed to the development of new classes of chemotherapy agents for over 40 years. The ... ...

Abstract	The diversity of natural compounds is essential for their mechanism of action. The source, structures and structure activity relationship of natural compounds contributed to the development of new classes of chemotherapy agents for over 40 years. The availability of combinatorial chemistry and high-throughput screening has fueled the challenge to identify novel compounds that mimic nature's chemistry and to predict their macromolecular targets. Combining conventional and targeted therapies helped to successfully overcome drug resistance and prolong disease-free survival. Here, we aim to provide an overview of preclinical investigated natural compounds alone and in combination to further improve personalization of cancer treatment.
MeSH term(s)	Antineoplastic Agents ; Biological Products ; Drug Design ; Humans ; Precision Medicine
Chemical Substances	Antineoplastic Agents ; Biological Products
Language	English
Publishing date	2018-05-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	47165-3
ISSN	1873-1899 ; 0734-9750
ISSN (online)	1873-1899
ISSN	0734-9750
DOI	10.1016/j.biotechadv.2018.04.009
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Zs.A 3730: Show issues

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Article: Phytochemical Screening and Antioxidant and Cytotoxic Effects of Acacia macrostachya

Ganamé, Hamidou Têeda / Karanga, Yssouf / Tapsoba, Issa / Dicato, Mario / Diederich, Marc F. / Cerella, Claudia / Sawadogo, Richard Wamtinga

Plants. 2021 July 02, v. 10, no. 7

2021

Abstract: Acacia macrostachya is used in Burkina Faso folk medicine for the treatment of inflammation and cancer. The purpose of this study was to evaluate the antioxidant and cytotoxic effects of this plant. The cytotoxic effects of root (dichloromethane B1 and ... ...

Abstract	Acacia macrostachya is used in Burkina Faso folk medicine for the treatment of inflammation and cancer. The purpose of this study was to evaluate the antioxidant and cytotoxic effects of this plant. The cytotoxic effects of root (dichloromethane B1 and methanol B2) and stem (dichloromethane B3 and methanol B4) bark extracts of A. macrostachya were assessed on chronic K562 and acute U937 myeloid leukemia cancer cells using trypan blue, Hoechst, and MitoTracker Red staining methods. The antioxidant content of extracts was evaluated using DPPH (2,2-diphenyl-1-picryl-hydrazyl) and FRAP (ferric reducing antioxidant power) methods. The root bark extracts B1 and B2 of A. macrostachya demonstrated higher cytotoxicity with IC₅₀ values in a low µg/mL range on both U937 and K562 cells, while the stem bark B4 extract selectively affected U937 cells. Overall, healthy proliferating peripheral blood mononuclear cells (pPBMCs) were not or barely impacted in the range of concentrations cytotoxic to cancer cells. In addition, A. macrostachya exhibited significant antioxidant content with 646.06 and 428.08 µg ET/mg of extract for the B4 and B2 extracts, respectively. Phytochemical screening showed the presence of flavonoids, tannins, alkaloids, and terpenoids/steroids. The results of this study highlight the interest of A. macrostachya extracts for the isolation of anticancer molecules.
Keywords	Acacia ; antioxidant activity ; antioxidants ; bark ; cytotoxicity ; flavonoids ; inflammation ; methanol ; methylene chloride ; myeloid leukemia ; terpenoids ; traditional medicine ; Burkina Faso
Language	English
Dates of publication	2021-0702
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants10071353
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Marine Polyether Phycotoxin Palytoxin Induces Apoptotic Cell Death via Mcl-1 and Bcl-2 Downregulation.

Kim, Jaemyun / Ji, Seungwon / Lee, Jin-Young / Lorquin, Jean / Orlikova-Boyer, Barbora / Cerella, Claudia / Mazumder, Aloran / Muller, Florian / Dicato, Mario / Detournay, Olivier / Diederich, Marc

Marine drugs

2023 Volume 21, Issue 4

Abstract: Palytoxin is considered one of the most potent biotoxins. As palytoxin-induced cancer cell death mechanisms remain to be elucidated, we investigated this effect on various leukemia and solid tumor cell lines at low picomolar concentrations. As palytoxin ... ...

Abstract	Palytoxin is considered one of the most potent biotoxins. As palytoxin-induced cancer cell death mechanisms remain to be elucidated, we investigated this effect on various leukemia and solid tumor cell lines at low picomolar concentrations. As palytoxin did not affect the viability of peripheral blood mononuclear cells (PBMC) from healthy donors and did not create systemic toxicity in zebrafish, we confirmed excellent differential toxicity. Cell death was characterized by a multi-parametric approach involving the detection of nuclear condensation and caspase activation assays. zVAD-sensitive apoptotic cell death was concomitant with a dose-dependent downregulation of antiapoptotic Bcl-2 family proteins Mcl-1 and Bcl-xL. Proteasome inhibitor MG-132 prevented the proteolysis of Mcl-1, whereas the three major proteasomal enzymatic activities were upregulated by palytoxin. Palytoxin-induced dephosphorylation of Bcl-2 further exacerbated the proapoptotic effect of Mcl-1 and Bcl-xL degradation in a range of leukemia cell lines. As okadaic acid rescued cell death triggered by palytoxin, protein phosphatase (PP)2A was involved in Bcl-2 dephosphorylation and induction of apoptosis by palytoxin. At a translational level, palytoxin abrogated the colony formation capacity of leukemia cell types. Moreover, palytoxin abrogated tumor formation in a zebrafish xenograft assay at concentrations between 10 and 30 pM. Altogether, we provide evidence of the role of palytoxin as a very potent and promising anti-leukemic agent, acting at low picomolar concentrations in cellulo and in vivo.
MeSH term(s)	Animals ; Humans ; Leukocytes, Mononuclear/metabolism ; Zebrafish/metabolism ; Down-Regulation ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism ; Cell Line, Tumor ; Leukemia ; bcl-X Protein/metabolism ; bcl-X Protein/pharmacology
Chemical Substances	palytoxin (OQ17NC0MOV) ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2 ; Apoptosis Regulatory Proteins ; bcl-X Protein
Language	English
Publishing date	2023-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175190-0
ISSN	1660-3397 ; 1660-3397
ISSN (online)	1660-3397
ISSN	1660-3397
DOI	10.3390/md21040233
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Article ; Online: ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides.

Cerella, Claudia / Gajulapalli, Sruthi Reddy / Lorant, Anne / Gerard, Deborah / Muller, Florian / Lee, Yejin / Kim, Kyung Rok / Han, Byung Woo / Christov, Christo / Récher, Christian / Sarry, Jean-Emmanuel / Dicato, Mario / Diederich, Marc

Leukemia

2023 Volume 38, Issue 1, Page(s) 67–81

Abstract: Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax ... ...

Abstract	Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML. Despite preclinical evidence, the repurposing of cardiac glycosides (CGs) in cancer therapy remained unsuccessful due to a lack of predictive biomarkers. We report that the ex vivo response of AML patient blasts and the in vitro sensitivity of established cell lines to the hemi-synthetic CG UNBS1450 correlates with the ATPase Na
MeSH term(s)	Humans ; Cardiac Glycosides ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Sulfonamides/pharmacology ; fms-Like Tyrosine Kinase 3/metabolism ; Cell Line, Tumor ; Sodium-Potassium-Exchanging ATPase/metabolism ; Sodium-Potassium-Exchanging ATPase/therapeutic use ; bcl-X Protein/metabolism
Chemical Substances	venetoclax (N54AIC43PW) ; Cardiac Glycosides ; Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; ATP1A1 protein, human (EC 3.6.1.-) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; BCL2L1 protein, human ; bcl-X Protein
Language	English
Publishing date	2023-10-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02076-8
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Zs.A 2295: Show issues

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Article ; Online: Cardiac glycosides: From molecular targets to immunogenic cell death.

Diederich, Marc / Muller, Florian / Cerella, Claudia

Biochemical pharmacology

2017 Volume 125, Page(s) 1–11

Abstract: Cardiac glycosides (CGs) are approved for the treatment of cardiovascular alterations and their known cellular target is the alpha subunit of the sodium ( ... ...

Abstract	Cardiac glycosides (CGs) are approved for the treatment of cardiovascular alterations and their known cellular target is the alpha subunit of the sodium (Na
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cardiac Glycosides/pharmacology ; Cell Death/drug effects ; Endocytosis/drug effects
Chemical Substances	Antineoplastic Agents ; Cardiac Glycosides
Language	English
Publishing date	2017-02-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2016.08.017
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