Targeted Cancer Therapy Using Compounds Activated by Light

SIMPLE SUMMARY: Cancer is among the leading causes of death, and cancer therapy suffers from many drawbacks, the lack of selectivity being most noteworthy. In this review, we present innovative approaches in the discovery of novel anticancer compounds, which can use light activation to achieve more potent cancer therapy with fewer side effects. We describe recent approaches to prepare photocages and photoswitches and obstacles that photopharmacology must overcome to achieve clinical use. ABSTRACT: Cancer chemotherapy is affected by a modest selectivity and toxic side effects of pharmacological interventions. Among novel approaches to overcome this limitation and to bring to therapy more potent and selective agents is the use of light for selective activation of anticancer compounds. In this review, we focus on the anticancer applications of two light-activated approaches still in the experimental phase: photoremovable protecting groups (“photocages”) and photoswitches. We describe the structural considerations behind the development of novel compounds and the plethora of assays used to confirm whether the photochemical and pharmacological properties are meeting the stringent criteria for an efficient in vivo light-dependent activation. Despite its immense potential, light activation brings many challenges, and the complexity of the task is very demanding. Currently, we are still deeply in the phase of pharmacological tools, but the vivid research and rapid development bring the light of hope for potential clinical use.