The role of ABCG2 in modulating responses to anti-cancer photodynamic therapy
M Ibrahim Khot1, Candice L Downey1, Gemma Armstrong1
1School of Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
Abstract:
The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transmembrane protein transporter is known for conferring resistance to treatment in cancers. Photodynamic therapy (PDT) is a promising anti-cancer method involving the use of light-activated photosensitisers to precisely induce oxidative stress and cell death in cancers. ABCG2 can efflux photosensitisers from out of cells, reducing the capacity of PDT and limiting the efficacy of treatment. Many studies have attempted to elucidate the relationship between the expression of ABCG2 in cancers, its effect on the cellular retention of photosensitisers and its impact on PDT. This review looks at the studies which investigate the effect of ABCG2 on a range of different photosensitisers in different pre-clinical models of cancer. This work also evaluates the approaches that are being investigated to address the role of ABCG2 in PDT with an outlook on potential clinical validation.
Insights
The ABCG2 transporter reduces cancer treatment effectiveness by removing photosensitizers used in photodynamic therapy (PDT). This review examines how ABCG2 impacts PDT efficacy and explores strategies to overcome this resistance.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transporter is implicated in cancer treatment resistance.
- Photodynamic therapy (PDT) utilizes photosensitizers to induce cancer cell death via light activation.
- ABCG2 efflux of photosensitizers compromises PDT efficacy.
Purpose of the Study:
- To review the impact of ABCG2 on photosensitizer retention and PDT efficacy across various preclinical cancer models.
- To evaluate strategies aimed at mitigating ABCG2-mediated resistance in PDT.
- To provide an outlook on the clinical validation of these strategies.
Main Methods:
- Literature review of studies investigating ABCG2 expression, photosensitizer retention, and PDT outcomes.
- Analysis of preclinical cancer models examining ABCG2's role in PDT.
- Evaluation of therapeutic approaches to overcome ABCG2-related PDT resistance.
Main Results:
- ABCG2 actively effluxes photosensitizers, diminishing their intracellular concentration and reducing PDT effectiveness.
- The level of ABCG2 expression correlates with reduced photosensitizer retention and poorer PDT outcomes.
- Various strategies are being explored to inhibit ABCG2 function or bypass its efflux mechanisms.
Conclusions:
- ABCG2 poses a significant challenge to effective photodynamic therapy in cancer treatment.
- Targeting ABCG2 or developing alternative therapeutic strategies is crucial for enhancing PDT efficacy.
- Further research and clinical validation are needed to translate these findings into improved cancer therapies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...