Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
Purpose of reviewTransurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic.
Recent findingsSeveral recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered.
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