Photochemotherapy

Photochemotherapy is treatment in which a light-absorbing drug is given first and then activated by light of a matched wavelength, so that the drug is inert until illumination and the effect is confined to the tissue exposed. Two distinct modalities share that description. In the classical sense the term denotes psoralen plus ultraviolet A (PUVA): psoralens intercalate into DNA and, on UVA exposure, form covalent adducts and interstrand crosslinks that suppress the proliferating and immune cells of the skin. This route needs no oxygen. In photodynamic therapy (PDT) the mechanism is different — a photosensitizer absorbs a photon and transfers the energy to molecular oxygen, generating singlet oxygen and other reactive oxygen species that damage membranes, organelles such as the mitochondrion and DNA, killing cells by apoptosis or necrosis. Because PDT consumes oxygen to work, hypoxic tissue resists it, a limitation PUVA does not share.

Both confer spatiotemporal control: cytotoxicity occurs only where drug and light coincide, which spares untreated tissue and largely avoids the systemic toxicity of chemotherapy or radiotherapy. The trade-off is reach — light penetrates a few millimetres of tissue, so accessible surfaces and cavities are treatable while deep or disseminated disease is not, and patients remain photosensitive until the drug clears.

PUVA is used for psoriasis, vitiligo, mycosis fungoides and other cutaneous T-cell lymphomas, and in extracorporeal photopheresis for graft-versus-host disease, where blood is treated outside the body and returned; long-term use raises skin cancer risk, which has narrowed its role since targeted immunomodulators appeared. PDT is established in oncology and dermatology for malignant disease of the skin, bladder cancer, and head and neck tumors, while applications in ovarian cancer, liver cancer, breast, colorectal and prostate tumors are predominantly investigational, and pre-cancerous lesions including those driven by high-risk human papillomavirus. It is also used against infection, eradicating bacteria in wounds and biofilms, where killing by short-lived oxidants rather than by a molecular target makes resistance difficult to acquire.