Targeting lineage plasticity in prostate cancer
Mené sur 169 patients atteints d'un cancer de la prostate résistant à la castration, cet essai de phase I/II évalue la dose maximale tolérée du carboplatine en ajout au cabazitaxel, puis analyse l'efficacité, du point de vue de la survie sans progression, de cette combinaison
In cancer biology, the term lineage plasticity denotes a process by which cancer cells change from one morphological and functional cell type to another (and back), under the influence of particular environmental pressures. In the context of prostate cancer therapy, lineage plasticity refers to a shift in cellular phenotype from an androgen receptor-dependent adenocarcinoma to an androgen receptor-indifferent neuroendocrine or small-cell carcinoma, which might occur as a consequence of ongoing androgen deprivation therapies. These neuroendocrine prostate cancers are difficult to define histologically (except in the case of pure small-cell prostate cancers) but are clinically characterised by inadequate responses to androgen deprivation therapy and novel hormonal therapies. Early data have suggested that patients with these neuroendocrine prostate tumours might also have suboptimal responses to taxane chemotherapies, perhaps showing greater sensitivity to platinum agents.
The Lancet Oncology , commentaire, 2018