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Pharmaceuticals
Special Issues
Drug Resistance Against Cancer Treatment
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Drug Resistance Against Cancer Treatment

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 2128

Special Issue Editor

Dr. Hamidreza Montazeri Aliabadi

E-Mail Website
Guest Editor
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA
Interests: pharmaceutics; targeted delivery; RNA interference; cancer biology; signaling pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the era when chemotherapy was the only option for “drug” therapy in cancer treatment, multidrug resistance (MDR) was a major hurdle that could suddenly render even the most effective treatments obsolete. In fact, MDR seemed to be so inevitable that it was known as a matter of “when”, rather than a matter of “if”. Chemotherapy is still at the forefront of cancer treatment, even following the introduction of molecularly targeted small molecule drugs, and therefore, the battle with MDR continues. While mechanisms involved in MDR might not apply to molecularly targeted drugs, the resistance to these drugs is also an ever-present threat. However, just like the drug itself, the resistance mechanisms (inherent or acquired) are more specific, often relating to the same signaling pathway that is the target of the drug.

This Special Issue aims to include research and review papers that provide the most recent information and developments on the ongoing battle with resistance against cancer treatment. The scope of the issue is to cover both MDR and resistance against molecularly targeted drugs. Our hope is to bring together a collective wisdom regarding our approach to drug resistance in cancer.

Dr. Hamidreza Montazeri Aliabadi
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. Pharmaceuticals 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 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 (MDR)
  • chemotherapy
  • P-glycoprotein (P-gp)
  • ATP-binding cassette (ABC) transporters
  • molecularly targeted drugs
  • inherent resistance
  • acquired resistance
  • signaling pathways

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Published Papers (2 papers)

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36 pages, 3205 KiB  
Review
Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf
by Abdulelah Alhazza, Adenike Oyegbesan, Emira Bousoik and Hamidreza Montazeri Aliabadi
Pharmaceuticals 2025, 18(6), 895; https://doi.org/10.3390/ph18060895 (registering DOI) - 14 Jun 2025
Abstract
After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent [...] Read more.
After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a variety of molecularly targeted drugs to clinical practice, chemotherapy is still at the forefront of the battle against cancer. In this manuscript, we review the major mechanisms involved in MDR and resistance against different categories of molecularly targeted drugs separately, and review some of the strategies studied to overcome the resistance against cancer therapy. While MDR mechanisms have been reviewed previously, the molecular mechanisms of resistance to the latest generations of anticancer drugs are rarely reviewed as a group, and the connection between the two categories of resistance is often missing in this type of publication. Our aim is to illustrate a comprehensive picture of what the landscape of cancer treatment is today with respect to resistance. While this picture seems bleak, and it is the common belief that resistance is inevitable, understanding the mechanisms involved could potentially lead to more efficient approaches to overcoming this so far unbeatable obstacle. Full article
(This article belongs to the Special Issue Drug Resistance Against Cancer Treatment)
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29 pages, 3627 KiB  
Systematic Review
Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma
by Brandon Wee Siang Phon, Shalini Sundramurthi Chelliah, Dina El-Rabie Osman, Saatheeyavaane Bhuvanendran, Ammu Kutty Radhakrishnan and Muhamad Noor Alfarizal Kamarudin
Pharmaceuticals 2025, 18(1), 102; https://doi.org/10.3390/ph18010102 - 15 Jan 2025
Cited by 1 | Viewed by 1426
Abstract
Background: The multiple drug-resistant phenomenon has long since plagued the effectiveness of various chemotherapies used in the treatment of patients with glioblastoma (GBM), which is still incurable to this day. ATP-binding cassette (ABC) transporters function as drug transporters and have been touted [...] Read more.
Background: The multiple drug-resistant phenomenon has long since plagued the effectiveness of various chemotherapies used in the treatment of patients with glioblastoma (GBM), which is still incurable to this day. ATP-binding cassette (ABC) transporters function as drug transporters and have been touted to be the main culprits in developing resistance to xenobiotic drugs in GBM. Methods: This review systematically analyzed the efficacy of ABC transporters against various anticancer drugs from 16 studies identified from five databases (PubMed, Medline, Embase, Scopus, and ScienceDirect). Results: Inhibition of ABC transporters, especially ABCB1, improved drug efficacies. Staple GBM phenotypes, such as GBM stem cells and increased activation of the PI3K/Akt/NF-κB pathway, have been implicated in the expression of several ABC transporters. Using the datasets in The Cancer Genome Atlas and Gene Expression Omnibus, we found upregulated ABC transporters that either negatively impacted survival in univariate analyses (ABCA1, ABCA13, ABCB9, ABCD4) or were independent negative prognosis factors for patients with GBM (ABCA13, ABCB9). Our multivariate analysis further demonstrated three ABC transporters, ABCA13 (Hazard Ratio (HR) = 1.31, p = 0.017), ABCB9 (HR = 1.26, p = 0.03), and ABCB5 (HR = 0.77, p = 0.016), with the administration of alkylating agents (HR = 0.41, p < 0.001), were independent negative prognosis factors for patients with GBM. Conclusions: These findings reinforce the important role played by ABC transporters, particularly by ABCA13, ABCB9, and ABCB1, which could be potential targets that warrant further evaluations for alternate strategies to augment the effects of existing alkylating agents and xenobiotic drugs. Full article
(This article belongs to the Special Issue Drug Resistance Against Cancer Treatment)
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