A light in multidrug resistance: Photodynamic treatment of multidrug-resistant tumors

Abstract

The major drawback of cancer chemotherapy is the development of multidrug-resistant (MDR) tumor cells, which are cross-resistant to a broad range of structurally and functionally unrelated agents, making it difficult to treat these tumors. In the last decade, a number of authors have studied the effects of photodynamic therapy (PDT), a combination of visible light with photosensitizing agents, on MDR cells. The results, although still inconclusive, have raised the possibility of treating MDR tumors by PDT. This review examines the growing literature concerning the responses of MDR cells to PDT, while stressing the need for the development of new photosensitizers that possess the necessary characteristics for the photodynamic treatment of this class of tumor.

Inativação fotodinâmica de microrganismos

“…Os fotossensibilizadores mais utilizados em TFD do câncer são os derivados de hematoporfirina sendo Photofrim ® (Canadá) o mais conhecido, tendo sido autorizado para uso clínico em 1998 nos Estados Unidos seguido por Canadá, Holanda, França, Alemanha, Japão etc 8 . Os fotossensibilizadores correspondentes produzidos na Alemanha e Rússia são, respectivamente, Photosan ® e Photogem ®45-47 .…”

“…Além disso, devido ao seu baixo risco, pode ser usado em pessoas idosas ou que estão debilitadas demais para serem submetidas a uma cirurgia. O principal efeito colateral é a sensibilização à luz, que é contornada evitando exposição à luz solar e luz interna muito intensa por um período de até 6 semanas, dependendo do FS 8 . De modo geral, o FS é injetado na corrente sanguínea e, dependendo do tipo de corante, é absorvido por células de todo o corpo.…”

“…A morte celular pode também ocorrer mediada por apoptose. TFD tem sido também usada com bons resultados contra tumores com o fenótipo chamado resistência a multifármacos (MDR), ou seja, resistente a uma grande variedade de fármacos estrutural e funcionalmente não relacionados 8 . TFD já foi aprovada para tratamento de vários tipos de câncer como de bexiga, pulmão, esôfago, gástrico e cervical, além de degeneração macular relacionada à idade.…”

Intracellular chemiluminescence activates targeted photodynamic destruction of leukaemic cells

“…This is probably due to the pathway of cell entry that involves receptor-mediated endocytosis, initial passage of the LTC to lysosomes and then release of the toxin component to other intracellular targets, such as the endoplasmic reticulum and nucleus. With regards to PDT, whereas this modality has been found effective against MDR tumour cells (Capella and Capella, 2003;Preise et al, 2003), very few studies have directly approached the possibility of resistance developing to repeated Ps exposure. Madsen et al (2003) for instance reported that no resistance developed in glioma spheroids repeatedly exposed to free 5-aminoelulinic acid but as we have shown that LTCs are much more effective than free Ps we subjected FL cells to several rounds of treatment with suboptimal doses of Tf -Hp does not induce the MDR phenomenon.…”

Can Photodynamic Therapy Be an Alternative Method in Melanoma Treatment?

“…In contrast to the other two it is independent of the dissolved oxygen in the tissue. The photosensitizer in the singlet excited state can react directly with biomolecules, inducing a process of photoadduct formation (Capella et al, 2003). However, this mechanism is often ignored because the electron transfer between a biomolecule and photosensitizer, and formation of free radicals, is not effective (Ochneser 1997).…”