methoxsalen

Overview

Methoxsalen (8-methoxypsoralen, 8-MOP) is a naturally occurring furocoumarin compound used as a photosensitizer in PUVA (psoralen + UVA) phototherapy. Upon UVA activation it intercalates into DNA and forms monofunctional adducts and interstrand crosslinks (primarily at TpA dinucleotides), inducing a characteristic mutational signature (PUVA signature). It is used clinically for psoriasis, vitiligo, and cutaneous T-cell lymphoma, but long-term PUVA therapy carries an increased risk of squamous cell carcinoma of the skin.

Evidence in the corpus

  • In ancillary in-vitro experiments supporting PMID:26950094, HaCaT keratinocytes were treated with 8-methoxypsoralen (methoxsalen) plus UVA and re-sequenced with NanoSeq; this reproduced a PUVA-associated mutational signature comprising SBS288A and SBS288B (the latter combining APOBEC SBS2/SBS13 features with T>A/T>C/T>G changes), validating the PUVA signature recovered in two psoriasis patients (patients 8 and 15) from the clinical NB-UVB cohort. Methoxsalen was used as a cell-line reagent, not as an intervention in patients. PMID:26950094

Resistance mechanisms

  • Not applicable (methoxsalen used as a photosensitizer, not as a therapeutic target in this corpus).

Cancer types (linked)

  • CSCC — squamous cell carcinoma of the skin; PUVA therapy is an established risk factor for cSCC; PUVA mutational signature (SBS288A/SBS288B) characterised in PMID:26950094.
  • BCC — basal cell carcinoma; mentioned as a surveillance target in the NB-UVB phototherapy study.

Sources

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