Resistance To Photodynamic Therapy For Cancer: Mechanisms, OriPins,ChallenPes And Solutions

Photodynamic therapy (PDT) is clinically approved, and a minimally invasive treatment methodthat can be apply selectively cytotoxic activity aPainst several types of cancer cells. PDT iscomposed of three essential components: photosensitizer (PS), oxyPen and liPht. The Anti-tumoreffects of PDT are obtained from three related mechanisms, includinP direct cytotoxic effects ontumor cells, tumor blood vessel damaPe and induce stronP inflammatory reaction that can lead tothe development of systemic immunity. DurinP PDT, reactive oxyPen species are produced and thusantioxidant defense mechanisms that play an important role to deal with injuries, induced andcauses activation of heat shock proteins (HSP). At later staPes, includes processes such as repairinPof protein s damaPes, activation of multiple paths to survive, induction of stress response Penesand Hypoxia. The Hypoxia leads to increased rates hypoxia-inducible factor 2 alpha (HIF2A), thatthis factor is mediatinP factor for the expression of Penes such as Oct4, NanoP and C-MYC, Whichmakes protects the cancer stem cells. Therefore, therapies that are effective at hypoxic conditionsin the microenvironment could potentially reduce the development of druP resistance and toprevent tumor recurrence. Lower rates of oxyPen consumption by PS, allowinP sufficient time forreplenishment of tumor’s oxyPen and prevent the rapid depletion of oxyPen. SwitchinP mechanismof free radical production from reaction type 2 to reaction type 1,Which is only sliPhtly dependenton oxyPen, that is fascinatinP stratePy to improve the effectiveness of PDT. UnderstandinP the basicmechanisms of resistance to PDT, will help to improve the efficacy of PDT and eventually achieve anew treatment protocol, which will lead to more efficient ways to treatment of patients. In thisreview, we examined the most important mechanisms of resistance to PDT, and focus on the recentstratePies based on nanotechnoloPy and stem cells for overcominP these mechanisms to improvePDT.