Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma
<b>Background</b>: 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 transport...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/102 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587727834447872 |
|---|---|
| author | Brandon Wee Siang Phon Shalini Sundramurthi Chelliah Dina El-Rabie Osman Saatheeyavaane Bhuvanendran Ammu Kutty Radhakrishnan Muhamad Noor Alfarizal Kamarudin |
| author_facet | Brandon Wee Siang Phon Shalini Sundramurthi Chelliah Dina El-Rabie Osman Saatheeyavaane Bhuvanendran Ammu Kutty Radhakrishnan Muhamad Noor Alfarizal Kamarudin |
| author_sort | Brandon Wee Siang Phon |
| collection | DOAJ |
| description | <b>Background</b>: 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. <b>Methods</b>: 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). <b>Results</b>: 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, <i>p</i> = 0.017), ABCB9 (HR = 1.26, <i>p</i> = 0.03), and ABCB5 (HR = 0.77, <i>p</i> = 0.016), with the administration of alkylating agents (HR = 0.41, <i>p</i> < 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. |
| format | Article |
| id | doaj-art-a307c2dd52b3494b9f6536165e820e58 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-a307c2dd52b3494b9f6536165e820e582025-01-24T13:45:24ZengMDPI AGPharmaceuticals1424-82472025-01-0118110210.3390/ph18010102Revisiting ABC Transporters and Their Clinical Significance in GlioblastomaBrandon Wee Siang Phon0Shalini Sundramurthi Chelliah1Dina El-Rabie Osman2Saatheeyavaane Bhuvanendran3Ammu Kutty Radhakrishnan4Muhamad Noor Alfarizal Kamarudin5Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia<b>Background</b>: 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. <b>Methods</b>: 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). <b>Results</b>: 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, <i>p</i> = 0.017), ABCB9 (HR = 1.26, <i>p</i> = 0.03), and ABCB5 (HR = 0.77, <i>p</i> = 0.016), with the administration of alkylating agents (HR = 0.41, <i>p</i> < 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.https://www.mdpi.com/1424-8247/18/1/102glioblastomaABC transportersdrug transportincreased drug efficacytemozolomidealkylating agents |
| spellingShingle | Brandon Wee Siang Phon Shalini Sundramurthi Chelliah Dina El-Rabie Osman Saatheeyavaane Bhuvanendran Ammu Kutty Radhakrishnan Muhamad Noor Alfarizal Kamarudin Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma Pharmaceuticals glioblastoma ABC transporters drug transport increased drug efficacy temozolomide alkylating agents |
| title | Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma |
| title_full | Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma |
| title_fullStr | Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma |
| title_full_unstemmed | Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma |
| title_short | Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma |
| title_sort | revisiting abc transporters and their clinical significance in glioblastoma |
| topic | glioblastoma ABC transporters drug transport increased drug efficacy temozolomide alkylating agents |
| url | https://www.mdpi.com/1424-8247/18/1/102 |
| work_keys_str_mv | AT brandonweesiangphon revisitingabctransportersandtheirclinicalsignificanceinglioblastoma AT shalinisundramurthichelliah revisitingabctransportersandtheirclinicalsignificanceinglioblastoma AT dinaelrabieosman revisitingabctransportersandtheirclinicalsignificanceinglioblastoma AT saatheeyavaanebhuvanendran revisitingabctransportersandtheirclinicalsignificanceinglioblastoma AT ammukuttyradhakrishnan revisitingabctransportersandtheirclinicalsignificanceinglioblastoma AT muhamadnooralfarizalkamarudin revisitingabctransportersandtheirclinicalsignificanceinglioblastoma |