Metallated phthalocyanines and their hydrophilic derivatives for multi-targeted oncological photodynamic therapy.

Background And Aim: A photosensitizer (PS) delivery and comprehensive tumor targeting platform was developed that is centered on the photosensitization of key pharmacological targets in solid tumors (cancer cells, tumor vascular endothelium, and cellular and non-cellular components of the tumor microenvironment) before photodynamic therapy (PDT). Interstitially targeted liposomes (ITLs) encapsulating zinc phthalocyanine (ZnPC) and aluminum phthalocyanine (AlPC) were formulated for passive targeting of the tumor microenvironment. In previous work it was established that the PEGylated ITLs were taken up by cultured cholangiocarcinoma cells.

Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.

Photodynamic therapy (PDT) is a minimally to noninvasive treatment modality that has emerged as a promising alternative to conventional cancer treatments. PDT induces hyperoxidative stress and disrupts cellular homeostasis in photosensitized cancer cells, resulting in cell death and ultimately removal of the tumor. However, various survival pathways can be activated in sublethally afflicted cancer cells following PDT.

Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.

Photodynamic therapy (PDT) is a non-to-minimally invasive treatment modality that utilizes photoactivatable drugs called photosensitizers to disrupt tumors with locally photoproduced reactive oxygen species (ROS). Photosensitizer activation by light results in hyperoxidative stress and subsequent tumor cell death, vascular shutdown and hypoxia, and an antitumor immune response. However, sublethally afflicted tumor cells initiate several survival mechanisms that account for decreased PDT efficacy.

Attritional evaluation of lipophilic and hydrophilic metallated phthalocyanines for oncological photodynamic therapy.

Background And Aim: Oncological photodynamic therapy (PDT) relies on photosensitizers (PSs) to photo-oxidatively destroy tumor cells. Currently approved PSs yield satisfactory results in superficial and easy-to-access tumors but are less suited for solid cancers in internal organs such as the biliary system and the pancreas. For these malignancies, second-generation PSs such as metallated phthalocyanines are more appropriate.

DNA methyltransferases expression in normal tissues and various human cancer cell lines, xenografts and tumors.

DNA methylation plays an important role in carcinogenesis and aberrant methylation patterns have been found in many tumors. Methylation is regulated by DNA methyltransferases (DNMT), catalyzing DNA methylation. Therefore inhibition of DNMT is an interesting target for anticancer treatment.

Transporter and Lysosomal Mediated (Multi)drug Resistance to Tyrosine Kinase Inhibitors and Potential Strategies to Overcome Resistance.

Tyrosine kinase inhibitors are a class of chemotherapeutic drugs that target specific protein kinases. These tyrosine kinase inhibitors constitute a relatively new class of drugs which target for instance Bcr-Abl, Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR). Despite some initial successes, the overall therapeutic benefit of tyrosine kinase inhibitors in the clinic has been mixed.