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New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors 2.0...
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New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors 2.0 (STRATAGEM Special Issue, EU-COST CA17104)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 7056

Special Issue Editors

Prof. Dr. Chiara Riganti

E-Mail Website
Guest Editor
Department of Oncology, University of Torino, via Santena 5/bis, 10126 Torino, Italy
Interests: multidrug resistance; immune-resistance; immune-evasion; cancer metabolism
Special Issues, Collections and Topics in MDPI journals
Dr. M. Helena Vasconcelos

E-Mail Website
Guest Editor
1. FFUP – Faculdade de Farmácia da Universidade do Porto, 4050-313 Porto, Potugal
2. i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
Interests: cancer drug resistance; cancer multidrug resistance; intercellular transfer of drug resistance mediated by Extracellular Vesicles (EVs); new approaches to overcome drug resistance; drug-efflux pumps; escape from apoptosis; autophagy; metabolic alterations associated with drug resistance; tumour-microenvironment interactions; cancer stem cells; microRNAs; biomarkers of minimal residual disease and of drug resistance
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Catherine Passirani

E-Mail Website
Guest Editor
1. Department of Pharmacy, University of Angers, 16 Boulevard Daviers, 49045 Angers, France
2. Micro et Nanomédecines Translationnelles, MINT, UNIV Angers, INSERM 1066, CNRS 6021, Angers, France
Interests: nanomedicine; lipid nanocapsules; ferrocifene; self-assemblies; active targeting; multidrug resistance; structure-property relationship
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Multidrug resistance (MDR) to cancer therapies often hinders the success of cancer treatment. Dealing with drug-resistant tumors requires a multidisciplinary approach. Indeed, only a better knowledge of the molecular basis of MDR could lead to the identification of new biomarkers and contribute to the design and formulation of new drugs tailored toward drug-resistant tumors. Testing the efficacy and verifying the safety of new drugs are key steps to move toward new therapeutic options for patients bearing drug resistant tumors. The European COST (Cooperation in Science and Technology) Action STRATAGEM—“New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors”—is the first multidisciplinary open consortium studying simultaneously the diagnostic, biological, pharmaceutical, therapeutic, and toxicological challenges related to MDR tumors.

Following the success of a previous Special Issue dedicated to manuscripts written by STRATAGEM members, this new Special Issue of Cancers aims to collect the latest original or review manuscripts on MDR in cancer, written by members of the STRATAGEM COST Action. Please note that this Special Issue is open only to members of STRATAGEM.

Prof. Dr. Chiara Riganti
Prof. Dr. M. Helena Vasconcelos
Prof. Dr. Catherine Passirani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multidrug resistance
  • ABC transporters
  • resistance to chemotherapy
  • resistance to immune-therapy
  • resistance to targeted therapies
  • drug tolerance
  • intercellular transfer of drug resistance traits mediated by extracellular vesicles (EVs)
  • tumor–microenvironment interactions
  • cancer stem cells
  • microRNAs
  • molecular targets
  • precision therapeutic strategies
  • personalized medicine
  • pharmacological strategies against resistant tumors
  • nanomedicine
  • active targeting
  • structure–activity relationship
  • drug repurposing
  • biomarkers of drug resistance
  • artificial intelligence applied to resistant tumors
  • OMIC techniques and big data analysis applied to drug resistance
  • computational biology
  • bioinformatic analysis of drug resistance data
  • toxicological studies of antitumor drugs
  • development of in silico tools and preclinical models to predict and test drug safety

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Published Papers (3 papers)

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Research

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15 pages, 2406 KiB  
Article
Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment
by Danijela Mandić, Lana Nežić, Ljiljana Amdžić, Nataša Vojinović, Radoslav Gajanin, Miroslav Popović, Jugoslav Đeri, Milena Todorović Balint, Jelena Dumanović, Zoran Milovanović, Jelica Grujić-Milanović, Ranko Škrbić and Vesna Jaćević
Cancers 2023, 15(16), 4106; https://doi.org/10.3390/cancers15164106 - 15 Aug 2023
Cited by 2 | Viewed by 1475
Abstract
Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if [...] Read more.
Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors 2.0 (STRATAGEM Special Issue, EU-COST CA17104))
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27 pages, 3598 KiB  
Article
Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance
by Vivien Pósa, Alessia Stefanelli, Julia H. Bormio Nunes, Sonja Hager, Marlene Mathuber, Nóra V. May, Walter Berger, Bernhard K. Keppler, Christian R. Kowol, Éva A. Enyedy and Petra Heffeter
Cancers 2022, 14(18), 4455; https://doi.org/10.3390/cancers14184455 - 14 Sep 2022
Cited by 16 | Viewed by 3246
Abstract
COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal [...] Read more.
COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal interaction properties of COTI-2 have not been investigated in detail so far. This is unexpected, as we have recently shown that COTI-2 forms stable ternary complexes with copper and glutathione, which renders this drug a substrate for the resistance efflux transporter ABCC1. Herein, the complex formation of COTI-2, two novel terminal N-disubstituted derivatives (COTI-NMe2 and COTI-NMeCy), and the non-substituted analogue (COTI-NH2) with iron, copper, and zinc ions was characterized in detail. Furthermore, their activities against drug-resistant cancer cells was investigated in comparison to COTI-2 and Triapine. These data revealed that, besides zinc, also iron and copper ions need to be considered to play a role in the mode of action and resistance development of these thiosemicarbazones. Moreover, we identified COTI-NMe2 as an interesting new drug candidate with improved anticancer activity and resistance profile. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors 2.0 (STRATAGEM Special Issue, EU-COST CA17104))
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Review

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28 pages, 6621 KiB  
Review
Thioredoxin Reductase and Organometallic Complexes: A Pivotal System to Tackle Multidrug Resistant Tumors?
by Michèle Salmain, Marie Gaschard, Milad Baroud, Elise Lepeltier, Gérard Jaouen, Catherine Passirani and Anne Vessières
Cancers 2023, 15(18), 4448; https://doi.org/10.3390/cancers15184448 - 6 Sep 2023
Cited by 3 | Viewed by 1380
Abstract
Cancers classified as multidrug-resistant (MDR) are a family of diseases with poor prognosis despite access to increasingly sophisticated treatments. Several mechanisms explain these resistances involving both tumor cells and their microenvironment. It is now recognized that a multi-targeting approach offers a promising strategy [...] Read more.
Cancers classified as multidrug-resistant (MDR) are a family of diseases with poor prognosis despite access to increasingly sophisticated treatments. Several mechanisms explain these resistances involving both tumor cells and their microenvironment. It is now recognized that a multi-targeting approach offers a promising strategy to treat these MDR tumors. Inhibition of thioredoxin reductase (TrxR), a key enzyme in maintaining redox balance in cells, is a well-identified target for this approach. Auranofin was the first inorganic gold complex to be described as a powerful inhibitor of TrxR. In this review, we will first recall the main results obtained with this metallodrug. Then, we will focus on organometallic complexes reported as TrxR inhibitors. These include gold(I), gold(III) complexes and metallocifens, i.e., organometallic complexes of Fe and Os derived from tamoxifen. In these families of complexes, similarities and differences in the molecular mechanisms of TrxR inhibition will be highlighted. Finally, the possible relationship between TrxR inhibition and cytotoxicity will be discussed and put into perspective with their mode of action. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors 2.0 (STRATAGEM Special Issue, EU-COST CA17104))
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