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Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The two approved porphyrin-based PDT agents, porfimer sodium (PhotofrinTM) and temoporfin (FoscanTM), are described below in more detail. Both are approved in most countries worldwide, and in the UK are recommended by NICE for cancer indications. The structurally similar agent verteporfin (VisudyneTM) is approved for the photodynamic treatment of age-related macular degeneration but not for cancer, although at the time of writing it is being investigated in the clinic for some cancer indications. Aminolevulinic acid and methyl aminolevulinate (MetvixTM; MetvixiaTM) are also described below. Between them they are approved by the FDA and EU for actinic keratosis (a precancerous skin condition), basal cell carcinoma, and the imaging of brain tumors. Finally, a new Antibody-drug conjugate (ADC) technology presently at the Phase 3 stage is described which consists of the EGFR-targeting antibody cetuximab chemically conjugated to an IR-activated dye as the cytotoxic payload.
Photodynamic therapy
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
Darius M Moshfeghi, Gholam A Peyman
Verteporfin PDT has proven itself to be an extraordinarily versatile therapy for management of subfoveal CNV of any etiology.59–;74 It has a favorable adverse-effects profile and appears to be well tolerated on retreatment.59–;74 While anti-VEGF therapies are on the horizon and hold great promise30–;32 (see Chapters 64 and 66–68), there is reason to presume that verteporfin will continue to be utilized both as primary therapy and in an adjunctive manner in many cases.31,75
Drug Targeting to the Lung: Chemical and Biochemical Considerations
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Peter A. Crooks, Narsimha R. Penthala, Abeer M. Al-Ghananeem
Pulmonary arterial hypertension (PAH) is a progressive lung disease characterized by an increase in blood pressure in the small arterioles that supply blood to the lungs. The underlying molecular and cellular mechanisms involved in PAH appear to be complex, with the pathophysiology suggesting a multifaceted disease in which cellular proliferation and vascular remodeling occurs, along with several other additional cellular mechanisms (Vaidya and Gupta 2015, Gaine and McLaughlin 2017). Combination therapy is now commonly used as the standard of care approach, with therapies that target three different pathogenic pathways. These therapies involve the use of drugs that target the endothelin and nitric oxide pathways, as well as the prostacyclin pathway (Malenfant et al. 2013, Lang and Gaine 2015). In recent studies (Bertero et al. 2016), it has been shown that in PAH-diseased lung tissue, dysregulation of vascular stiffness and cellular metabolism mechanoactivates the transcriptional coactivators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ)-dependent glutaminolysis, to drive PAH. These studies indicate that targeting this pathology with drugs such as the glutaminase inhibitor, CB-839 (Gross et al. 2014) or the YAP inhibitor, verteporfin (King et al. 2014) may prove beneficial in this disease. CB-839 is currently undergoing active clinical development in early clinical trials for cancer therapy, and verteporfin is already approved by the FDA for treatment of age-related macular degeneration (Kent 2014).
Trial watch: an update of clinical advances in photodynamic therapy and its immunoadjuvant properties for cancer treatment
Published in OncoImmunology, 2023
Mafalda Penetra, Luís G. Arnaut, Lígia C. Gomes-da-Silva
Although without clinical indication for cancer treatment, verteporfin (Visudyne®) should be mentioned owing to its success for the treatment of age-related macular degeneration (AMD) both in USA and in Europe (2000)29. Considering that the target is the ocular vasculature, verteporfin activation is conducted immediately 15 min after its administration (vascular-PDT). Verteporfin has a peak of absorption at 689 nm (ε692 nm = 13500 M−1cm−1 in PBS) and an elimination half-life of 5–6 h, which reduces the period of skin photosensitivity to less than 48 h30,31. Verteporfin has been evaluated for the treatment of cancer (namely non-melanoma skin and pancreas cancer) in numerous clinical trials32.
Quantitative Evaluation of Retinal Vessel Density in Central Serous Chorioretinopathy after Half-dose Photodynamic Therapy
Published in Current Eye Research, 2021
Fabao Xu, Lijun Zhou, Kunbei Lai, Yajun Gong, Longhui Li, Ping Lian, Chuangxin Huang, Xiaoyan Ding, Lin Lu, Chenjin Jin
Hd-PDT was performed when an active leakage and SRD involving fovea were present; Greatest linear dimension (GLD) was determined with reference to the area of abnormal choroidal circulation, such as hyperpermeability and dilated choroidal vessels according to ICGA.20 The treatment field size was set as 500 microns plus the GLD, with a minimum size of 3000 microns (the diameter of the laser spot). In practice, almost all cases were performed with a 3000 microns laser spot, with only one patient having 4200 microns because of two existing hyperpermeabilities near the fovea on ICGA. Verteporfin (Visudyne; Novartis, Switzerland) was administrated intravenously at a dose of 3 mg/m2 over 10 minutes. Fifteen minutes after commencing the verteporfin infusion, a contact lens (Volk® area centralis) was positioned on the affected eye, the treatment area was exposed to a 689 nm laser with a fluence of 600 mw/cm2 for 83 seconds and a total laser energy of 50 J/cm2.
Future concepts and therapy approaches for Peyronie’s disease
Published in Expert Opinion on Orphan Drugs, 2020
Edward J. Choi, Douglas Schneider, Perry Xu, Farouk M. El-Khatib, Faysal A. Yafi
There is active development of emerging, investigative therapies for PD, with many attempting to target the inflammatory cytokines that contribute to fibrosis in PD. In an in-vitro model, a Rho-kinase inhibitor in combination with simvastatin was shown to prevent TGF-β mediated myofibroblast differentiation by inhibiting the pro-fibrotic Yes‐Associated Protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) pathways [105]. Similarly, verteporfin, a treatment for macular degeneration, has been shown to inhibit fibrosis in Dupuytren's disease by inhibiting the downstream processes in the YAP pathway [106]. Vactosertib, an activin receptor-like kinase-5, was studied in a rat model of PD as well as human PD plaques in vitro to inhibit the TGF-β type I receptor, which resulted in reduced signs of inflammation and myofibroblast transformation [107]. Mycophenolate mofetil, an immunosuppressant, appears to reverse the fibrotic effects of TGF-β injected into rat tunica albuginea [108]. These novel studies provide a deeper understanding of the genetic and molecular pathophysiology of PD, but much more work remains before these potential therapeutic targets can be considered for clinical trials.