A Step Forward for Therapeutic Strategies in Prostate Cancer

Jeff holst

Dr Qian Wang (right) with colleague, Dr Jeff Holst (left).

In a study reported in the Journal of the National Cancer Institute, Qian Wang, PhD, of the Origins of Cancer Laboratory, Centenary Institute, and colleagues assessed the role of the amino acid transporter LAT3’s function in prostate cancer.

What happened?

They found that inhibition of LAT transporters, and thus leucine uptake, may constitute a new strategy for treatment of metastatic castration-resistant prostate cancer.

In the study, LAT3 protein expression was assessed in human prostate cancer tissue, which contained samples from patients with prostatic intraepithelial neoplasia or Gleason-graded prostate cancer and from patients at different stages after neoadjuvant hormone therapy.

Dr Qian Wang says, “Targeting LAT transporters, thereby inhibiting leucine uptake, may offer a new therapeutic opportunity for metastatic [castration-resistant prostate cancer], affecting tumor growth and metastasis.”

How does this work?

The authors draw attention to the reliance of cancer cells on amino acids and the subsequent nutrient transporters that supply tumors with leucine as metabolic fuel, which aids tumor growth.

Researchers can target amino acid transporters that are broken down into various families, such as LAT, in order to mediate the transport of amino acids to the tumors.

The importance of the LAT transporters has been evaluated in preclinical experiments in multiple cancer cell lines,2 and this study expands upon previous work by Holst and colleagues3 illustrating the importance of LAT1 and LAT3 in prostate cancer growth and oncogenesis.

The authors suggest that targeting LAT transporters, and thus influencing the uptake of leucine, affects tumor growth and metastasis. Consequently, these transporters are potential therapeutic targets in the treatment of advanced prostate cancer, including castration-resistant disease.

Clinical Impact

“While all data reported by Wang and colleagues are preclinical, inhibition of amino acid transporters is an exciting potential therapeutic target in prostate cancer,” according to Elizabeth R. Kessler, MD, and E. David Crawford, MD.

Treatment options for metastatic prostate cancer have expanded markedly in the last few years. However, the majority of these newer therapies, similar to existing therapies, are aimed at decreasing circulating testosterone or blocking the effects of testosterone (androgen receptor blockade).

Although these newer therapies may improve on current drugs that block the effects of testosterone, it has been found that the response to subsequent therapies is diminished.

This suggests that prostate cancer cells, much like any cancer cell, adapt to rely on varied growth mechanisms and continued mutagenesis for survival.

Targeting the LAT transporters is a potential new mechanism to control advanced prostate cancer.

What this means – future considerations

While all data reported by Wang and colleagues are preclinical, inhibition of amino acid transporters is an exciting potential therapeutic target in prostate cancer.

As our knowledge of the biology of castration-resistant prostate cancer evolves, we will need to rely on identification and the effective blockade of other pathways to stop tumor growth.

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