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But now, UC Davis Health researchers have developed a new compound that could offer alternatives for patients with treatment-resistant tumors. The molecule is called LX-1. It simultaneously targets androgen receptor (AR) variants and the enzyme AKR1C3, which are both known to drive resistance.
“Prostate tumors can develop multiple resistance mechanisms that allow them to live without external androgen, negating efforts to treat them,” said Director of Urologic Research Allen Gao, who is also the Ralph de Vere White Professor. “Once resistance develops, patients have few therapeutic choices, and their survival rate is quite poor.”
Normally, androgen receptors need androgen to be activated. But these AR variants are active all the time, driving tumor growth even without androgen stimulation.
Prostate tumors have other tricks to evade treatment. In the face of androgen deprivation, they can even make their own androgen, creating a closed circuit that defies intervention. Tumors often hijack AKR1C3 to make androgens.
Reversal of Apalutamide and Darolutamide Aldo-Keto Reductase 1C3-Mediated Resistance by a Small Molecule Inhibitor. 2020 Mar 3
Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells
