Metastatic Castration-Resistant Prostate Cancer Hungers for Leucine

Extract

Unfortunately, the current treatment for metastatic castration-resistant prostate cancer remains mostly palliative with little additional benefit. In this issue of the Journal, Wang and colleagues ( 1 ) present a landmark article that uncovers the Achilles heel of prostate cancer, which is cleverly disguised as the system L-type transporters (LATs). The LATs are amino acid exchangers that import the branched chain amino acids (such as leucine) in exchange for other intracellular amino acids (such as glutamine). The “Warburg effect” is a term often used to describe cancer cells that have an adapted metabolic profile. Such cancer cells have enhanced glucose uptake and even in the presence of oxygen, glucose is rapidly broken down by anaerobic metabolism. In a manner analogous to the dependency upon glucose in the Warburg effect, metastatic prostate cancer has an appetite for leucine. The research led by Dr. Jeff Holst reveals that metastatic castration-resistant prostate cancer cells are highly dependent on amino acid uptake through LATs for their growth and proliferation, as well as their malignant transformation ( 1 ). Discovery of this leucine hunger in metastatic prostate cancer (or, if I can be prudent and say the “Holst effect”), opens up a new therapeutic option to treat prostate cancer by inhibiting amino acid transporters.