Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances

Ebrahimi, Safieh; Khaleghi Ghadiri, Maryam; Stummer, Walter; Gorji, Ali

doi:10.1016/j.lfs.2024.122808

Life Sciences

2024

DOI: 10.1016/j.lfs.2024.122808

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Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances

Safieh Ebrahimi,

Maryam Khaleghi Ghadiri,

Walter Stummer

et al.

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Uncovering Porphyrin Accumulation in the Tumor Microenvironment

Adapa,

Sami,

Meshram

et al. 2024

Genes

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Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed “Porphyrin Overdrive”. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME’s stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention.

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Uncovering Porphyrin Accumulation in the Tumor Microenvironment

Adapa,

Sami,

Meshram

et al. 2024

Genes

View full text Add to dashboard Cite

show abstract

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Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances

Cited by 1 publication

References 183 publications

Uncovering Porphyrin Accumulation in the Tumor Microenvironment

Uncovering Porphyrin Accumulation in the Tumor Microenvironment

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