The word malignant comes from malignare, a Latin verb that means to intend to do evil. The ultimate evil is death. A cancerous tumor is called a malignancy because it causes death. As kids, cartoons and comic books show that evil villains are out to destroy the good guys, but there are either a) clever characters who elude the villain (think of Roadrunner outwitting Wile E. Coyote, or b) superheroes who save the day (think of Batman saving Gotham City from the malicious Joker).

Prostate cancer (PCa) is the most common malignancy among men. The type of PCa which is diagnosed most often (about 85% of cases) is called adenocarcinoma. It is usually found when it is at a nonaggressive low grade, and treatment success rates are very high. There are also rarer types of PCa that are highly aggressive out of the starting gate, such as ductal adenocarcinoma or mucinous PCa, but this blog only concerns how common adenocarcinoma can become frighteningly evil.

Localized adenocarcinoma can be conquered because it is still contained in the gland. Nonetheless, its nature is still malignant. Left untreated and unmonitored, it gradually increases in size (growth) and aggressiveness (progression). No matter how slowly these processes occur, common adenocarcinoma can become life-threatening through reproducing ever more cells, and some cells mutating in a more dangerous adenocarcinoma. These are normal cancer behaviors that overlap and feed into each other, so even the tamest adenocarcinoma can escape the gland and then inevitably spread to other sites. Now villain has eluded efforts to outwit it, and there is no superhero that can rescue its victim. At this stage, treatments can extend, but not save, life.

A newly discovered dark side

Scientists have now found what may be adenocarcinoma’s darkest side yet. A Dec. 2023 published paper describes a “trans-differentiation” of adenocarcinoma cells into a rare, treatment-resistant type called a small cell neuroendocrine (SCN) cancer. Through molecular reprogramming of genomic factors, the adenocarcinoma literally transforms into a highly dangerous malignancy.^[i] The researchers found that there were two, but only two, distinct pathways by which this transformation happens. This is breakthrough research:

SCN cancers make up only a small percentage of all newly diagnosed prostate cancers, but are more common among tumors that continue to grow after treatment. In both cases, SCN prostate cancers are especially fast-growing and difficult to treat. While researchers have previously identified the molecular differences between more common prostate adenocarcinomas and SCN cancers, they haven’t understood how those changes occurred.^[ii]

There is no question that SCN prostate cancers possess the darkest side of the prostate cancer force, a black magic ability to change a potentially treatable disease into an incurable one. The importance of this discovery lies in identifying exactly how these changes arise at the cellular level. It has implications for predicting which PCa patients may be vulnerable to either pathway of trans-differentiation, and developing drugs that target and prevent it from beginning.

It is not an overstatement to say that the researchers who designed and implemented this study are modern day superheroes. They have provided a means by which future studies will devise ways to outwit a previously unidentified villain, thereby rescuing the lives of untold victims from its evil intent.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Chen CC, Tran W, Song K, Sugimoto T et al. Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation. Cancer Cell. 2023 Dec 11;41(12):2066-2082.e9.
[ii] Williams, Sarah C.P. “UCLA researchers explain how prostate cancers grow more aggressively to evade treatment.” UCLA news release, Nov. 29, 2023. https://newsroom.ucla.edu/releases/study-prostate-cancers-grow aggressively-evade-treatment