Biotech Drug Shown to Kill Prostate Tumor Cells

(PDPics, Pixabay)

14 Feb. 2023. Tests with lab mice show low doses of an experimental oral drug can selectively kill prostate cancer cells while not affecting surrounding healthy tissue. A team from the biotechnology company Halda Therapeutics Inc., developer of a process for killing cancer cells while preventing resistance to the treatments, is presenting the results in a poster later this week at a meeting of American Society of Clinical Oncology.

Halda Therapeutics is a five year-old enterprise in New Haven, Connecticut, spun-off from the lab of its founder Craig Crews, a professor of biology, chemistry, and pharmacology at Yale University. Crews and colleagues study biochemical processes for degrading targeted proteins with what the lab calls proteolysis targeting chimeras or Protacs. These Protacs use another group of proteins in the body called E3 ubiquitin ligases to short-cut the quality-control mechanisms between cells, resulting in degradation of the protein targets.

Halda Therapeutics says they take Protacs one step further for cancer protein targets, in a process called Regulated Induced Proximity TArgeting Chimeras or Riptacs. The company says in Riptacs, the targeted cancer protein is weakly linked to an essential protein for the cell to survive, which when bound this way in close proximity, act as a cell-killing agent. For prostate cancer, the Riptac targets androgen receptor proteins found in male reproductive tissue and responsible for the growth of cancer in the prostate. In addition, says Halda, resistance to androgen receptor signaling inhibitors occurs in nearly all prostate cancer patients, as a result of genomic changes in the androgen receptor gene.

Second-leading cause of cancer death in men

Prostate cancer is the second-most common cancer among men, after skin cancer. American Cancer Society says one in eight men will be diagnosed with prostate cancer during their lifetimes. This year, the organization expects more than 288,000 cases in the U.S., leading to nearly 35,000 deaths. Prostate cancer is the second-leading cause of cancer death among men, after lung cancer.

In their study, a team led by Halda Therapeutics senior biologist Kanak Raina tested a small-molecule Riptac, first in prostate cancer cell lines and then formulated as an oral drug in castrated lab mice grafted with human prostate cancer. In lab cultures, reports the company, low concentrations of a Riptac compound kill prostate cancer cells while sparing non-cancerous control cells. In lab mice grafted with prostate cancer, a low dose of the Riptac compound targeting androgen receptors and formulated as an oral drug accumulates in the tumors and attacks only the cancer cells, not healthy tissue.

The Riptac drug for castration-resistant prostate cancer is Halda Therapeutics’ lead product. The company says other preclinical data show its prostate cancer therapy demonstrates anti-cancer activity superior to enzalutamide, a current drug approved to treat metastatic prostate cancer. Halda expects to file an investigational new drug application, in effect a request to begin clinical trials, with the Food and Drug Administration next year.

“Riptac therapeutics address a shortcoming shared by most current pharmaceutical modalities,” says Crews in a Halda Therapeutics statement, “namely, the reliance on oncogenic driver proteins which can result in drug resistance. This modality offers an oral, selective, and widely applicable cancer cell-killing mechanism that can overcome drug resistance and can be used in advanced cancer where resistance has emerged, as well as potentially in early-stage cancer.”

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