A novel drug candidate, QED-203, developed by the University of Queensland is moving toward clinical stage, offering a potential new line of attack against advanced prostate cancer, especially for men whose disease has become resistant to treatments. Scientists report this first-in-class small molecule targets a previously unexploited mechanism in cancer cells, potentially sidestepping the common issue of hormonal therapy resistance.

The focus of QED-203 is a protein called TRPV6, a type of calcium channel that researchers have dubbed an “oncochannel” due to its overexpression in prostate and other epithelial cancers, where it fuels tumor growth. Early studies demonstrate that QED-203 effectively blocks this channel at very low concentrations, choking off the calcium influx that cancer cells crave. This interference has been shown to disrupt critical signaling pathways within the cancer cells, including the NFAT and WNT pathways, which are known to drive cancer progression.

The downstream effects on prostate cancer cells are significant, according to the preclinical data. Treatment with QED-203 reportedly triggers endoplasmic reticulum stress, a condition that can lead to cell death, and importantly, it halts the relentless division of cancer cells, a process known as cell cycle arrest. Furthermore, the compound actively pushes cancer cells towards apoptosis, or programmed cell death, effectively causing them to self-destruct.

Perhaps most compelling is QED-203’s performance against treatment-resistant forms of the disease. Laboratory tests have shown it retains its power to inhibit cancer cell growth even in cell lines that no longer respond to enzalutamide, a widely used androgen receptor targeting agent. Strikingly, QED-203 demonstrated superior potency over both enzalutamide and darolutamide, when tested against prostate cancer cells carrying specific mutations in the androgen receptor or the particularly troublesome ARV7 splice variant. This ARV7 variant is a notorious culprit in rendering many current therapies ineffective for a significant number of patients.

Beyond its cellular impact, QED-203 appears to have characteristics that make it a viable candidate for patient use. Animal studies in rodents have indicated that the drug is well tolerated. In mouse models of prostate cancer, QED-203 showed efficacy in inhibiting tumor growth and reducing PSA levels comparable to that of enzalutamide. Researchers also confirmed the drug was hitting its intended TRPV6 target in these animal studies by observing changes in urine calcium levels and specific gene activity in tumors.

As a non-hormonal agent, QED-203 represents a fresh approach for patients who have exhausted options targeting the androgen receptor pathway.

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