Cancer stem cell populations exhibit resistances to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) which undermines the effectiveness of this treatment.
A recent study has unveiled concerning insights about cancer treatment using photodynamic therapy (PDT). Specifically, it focused on the role of cancer stem cells (CSCs) and their notable resistance to 5-aminolevulinic acid-derived PDT, prompting researchers to reevaluate the effectiveness of this widely used treatment method.
PDT, known as a minimally invasive cancer treatment, deploys photosensitizers like 5-aminolevulinic acid, which is absorbed by cancer cells and, upon light activation, generates reactive oxygen species (ROS) to instigate cell death. While PDT has demonstrated efficacy, previous observations noted survival rates of about 5-10% among treated cancer cells, highlighting the persistence of resistant populations post-treatment.
Investigators embarked on this research to determine if CSCs, increasingly recognized for driving resistance to various cancer therapies, also pose challenges during 5-ALA-PDT. The objective was clear: confirm if these stem cells were less susceptible to this form of treatment, thereby potentially contributing to recurrent tumor forms.
During the study, three distinct cancer cell lines were cultivated—human lung cancer (H1299), human breast cancer (Hs578T), and human colon cancer (DLD-1)—and subjected to 5-ALA-PDT. It was found alarming yet not surprising: CSL populations emerged as resistant to the treatment suggested by observed survival rates.
For example, the CD133+ stem cell subpopulation, which serves as a marker for CSCs, increased after exposure to 5-ALA-PDT across tested cell lines. Specifically, within DLD-1 cells, the percentage of viable CD133+ cells remained significantly high post-treatment, with only minor decreases compared to their total counterparts. Similar results underscored this phenomenon across the H1299 and Hs578T lines as well.
The researchers theorized the resistance of these stem cell populations is due to heightened expression of ATP-binding cassette (ABC) transporters, which are known to extrude therapeutic agents, reducing their efficacy. Supporting these findings, the study highlighted decreased accumulation of the photosensitizer protoporphyrin IX (PPIX) within CSCs, which is pivotal for the effectiveness of PDT because it directly correlates with cell susceptibility to treatment.
This research raises ethical and practical questions for the implementation of 5-ALA-PDT as it reveals potential pitfalls among the resistant CSCs. Author C.P.J. Rice noted, "Our results indicate CSCs are not sensitive to 5-ALA-PDT, which may contribute to the establishment of 5-ALA-PDT resistance." The authors advocate for the development of strategies aimed at boosting the effective targeting of CSCs during PDT to mitigate risks of cancer recurrence and improve overall treatment outcomes.
With the challenge of CSCs proving to be more formidable than anticipated, the authors urge scientific advancements to integrate therapies capable of overcoming this veil of resistance.
Future investigations are now beckoning to clarify how key mechanisms tied to these stem cells can be effectively counteracted to reinforce treatment options like PDT. The potential integration of innovative drugs with pediatric transporter inhibitors could yield beneficial outcomes for patients fighting cancer.