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Biomedicines
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Multidrug Resistance in Cancer: Genetic and Protein Biomarkers and Tools...
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Multidrug Resistance in Cancer: Genetic and Protein Biomarkers and Tools to Overcome MDR in Patients and Experimental Models

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 4312

Special Issue Editor

Dr. Radka Vaclavikova

E-Mail Website
Guest Editor
1. Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague 10, Czech Republic
2. Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic
Interests: ovarian cancer; breast cancer; renal cell cancer; biomarkers; biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor multidrug resistance (MDR) is one of the most important impediments in the treatment of cancer. MDR is formed against a broad variety of many structurally and mechanistically different anticancer drugs. Finding MDR determinants and tools to overcome this phenomenon is necessary to improve the treatment of resistant tumors. At present, many studies using standardized genomic and proteomic profiling approaches have led to the discovery of molecular and protein biomarkers of therapeutic response and MDR in solid tumor patients. In addition to identifying the MDR profile, discovery of new therapeutic targets, MDR-reversal agents and drugs that are effective in resistant tumor cells present a promising approach for the treatment of resistant tumors.  

This Special Issue of Biomedicines focuses on recent original findings, characterization, translation, and clinical application of cancer genetic or proteomic biomarkers of resistance and therapeutic outcomes in solid tumor patients and experimental models. In the frame of MDR research, this issue also focuses on identification and characterization of potential and effective tools to overcome the phenomenon of MDR in solid tumors. 

We cordially invite authors in this exciting field to submit original research or review articles contributing to the identification, clarification and overcoming of multidrug resistance as a main obstacle in successful treatment outcomes in patients with solid tumors.

Dr. Radka Vaclavikova
Guest Editor

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 short 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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • cancer
  • multidrug resistance
  • biomarkers
  • genomics
  • transcriptomics
  • proteomics
  • MDR-reversal agents
  • solid tumor patients in vitro and in vivo models

Published Papers (1 paper)

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Research

28 pages, 6808 KiB  
Article
Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells
by Sergei Boichuk, Pavel Dunaev, Ilshat Mustafin, Shinjit Mani, Kirill Syuzov, Elena Valeeva, Firuza Bikinieva and Aigul Galembikova
Biomedicines 2022, 10(3), 601; https://doi.org/10.3390/biomedicines10030601 - 03 Mar 2022
Cited by 18 | Viewed by 3785
Abstract
The microtubule-targeting agents (MTAs) are well-known chemotherapeutic agents commonly used for therapy of a broad spectrum of human malignancies, exhibiting epithelial origin, including breast, lung, and prostate cancer. Despite the impressive response rates shortly after initiation of MTA-based therapy, the vast majority of [...] Read more.
The microtubule-targeting agents (MTAs) are well-known chemotherapeutic agents commonly used for therapy of a broad spectrum of human malignancies, exhibiting epithelial origin, including breast, lung, and prostate cancer. Despite the impressive response rates shortly after initiation of MTA-based therapy, the vast majority of human malignancies develop resistance to MTAs due to the different mechanisms. Here, we report that infigratinib (BGJ 398), a potent FGFR1-4 inhibitor, restores sensitivity of a broad spectrum of ABCB1-overexpressing cancer cells to certain chemotherapeutic agents, including paclitaxel (PTX) and doxorubicin (Dox). This was evidenced for the triple-negative breast cancer (TNBC), and gastrointestinal stromal tumor (GIST) cell lines, as well. Indeed, when MDR-overexpressing cancer cells were treated with a combination of BGJ 398 and PTX (or Dox), we observed a significant increase of apoptosis which was evidenced by an increased expression of cleaved forms of PARP, caspase-3, and increased numbers of Annexin V-positive cells, as well. Moreover, BGJ 398 used in combination with PTX significantly decreased the viability and proliferation of the resistant cancer cells. As expected, no apoptosis was found in ABCB1-overexpressing cancer cells treated with PTX, Dox, or BGJ 398 alone. Inhibition of FGFR-signaling by BGJ 398 was evidenced by the decreased expression of phosphorylated (i.e., activated) forms of FGFR and FRS-2, a well-known adaptor protein of FGFR signaling, and downstream signaling molecules (e.g., STAT-1, -3, and S6). In contrast, expression of MDR-related ABC-transporters did not change after BGJ 398 treatment, thereby suggesting an impaired function of MDR-related ABC-transporters. By using the fluorescent-labeled chemotherapeutic agent PTX-Alexa488 (Flutax-2) and doxorubicin, exhibiting an intrinsic fluorescence, we found that BGJ 398 substantially impairs their efflux from MDR-overexpressing TNBC cells. Moreover, the efflux of Calcein AM, a well-known substrate for ABCB1, was also significantly impaired in BGJ 398-treated cancer cells, thereby suggesting the ABCB1 as a novel molecular target for BGJ 398. Of note, PD 173074, a potent FGFR1 and VEGFR2 inhibitor failed to retain chemotherapeutic agents inside ABCB1-overexpressing cells. This was consistent with the inability of PD 173074 to sensitize Tx-R cancer cells to PTX and Dox. Collectively, we show here for the first time that BGJ 398 reverses the sensitivity of MDR-overexpressing cancer cells to certain chemotherapeutic agents due to inhibition of their efflux from cancer cells via ABCB1-mediated mechanism. Full article
(This article belongs to the Special Issue Multidrug Resistance in Cancer: Genetic and Protein Biomarkers and Tools to Overcome MDR in Patients and Experimental Models)
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