Author: NEJM Frontiers in Medicine
Which is the only organ in a man's body that sustains lifelong growth?
The answer is, prostate.
Its growth process is fast and slow, growing rapidly in adolescence, entering the middle-aged and elderly and ushering in the "second spring". In some elderly men's bodies, it grows too big without paying attention, and it becomes commonly referred to as prostatic hyperplasia. However, a prostate that looks a little "excessive" is not life-threatening.
1. Prostate cancer: the incidence of malignant tumors in men ranks 6th
In contrast, prostate cancer is a malignant cell hyperplasia, ranking first in the incidence of malignant tumors in men for many years in Europe and the United States.
Although the incidence of prostate cancer in mainland China is lower than that in Europe and the United States, prostate cancer has become more and more common due to the intensification of population aging, improved diagnosis rate and lifestyle changes in recent years. According to the 2015 China Cancer Annual Report, prostate cancer ranks 6th in the incidence of malignant tumors in men.
At present, the treatment of prostate cancer is mainly to inhibit the secretion of androgens in patients, but the sustainability is not strong, and the tumor is easy to develop into "castration-resistant prostate cancer", that is, resistance to hormone therapy.
The researchers have developed a new therapy to disable cancer cell signaling by controlling androgen receptors. Recently, the New England Journal of Medicine, a top international journal, published the results of a Phase 3 clinical trial of Nzaluamine.
As one of the representative drugs of the new therapy, how is its clinical effect?
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Buffett and Murdoch are beneficiaries: suppressing androgens and stopping the supply of "fuel"
Although the pathogenesis of prostate cancer is not well understood, androgens seem to be inseparable.
In 1941, American surgeon Charles Brenton Huggins and others found that the use of surgical removal of the testicles to suppress androgen production, or estrogen supplementation to block androgen receptors, can be extremely effective in controlling prostate cancer. And if these patients, who have improved, are injected with androgens again, the cancer cells will become active again.
In this way, androgens seem to be the "fuel" for cancer cells – as long as the fuel supply is stopped, prostate cancer cannot continue to move forward.
For this important discovery, Charles Brenton Huggins won the 1966 Nobel Prize in Physiology or Medicine, a hormone therapy that came to be known as "androgen deprive therapy" (ADT) and has long been the treatment of choice for prostate cancer. It helps most patients to truly achieve "survival with tumors" or "coexistence with tumors", and Buffett and media tycoon Murdoch are the beneficiaries.
Unfortunately, in some cancer patients, androgen deprivation therapy can only alleviate prostate cancer for 2 to 3 years. This is because the cunning cancer cells have gradually found a countermeasure and can still make waves without "fuel". The disease inevitably progresses to "castration-resistant prostate cancer," which is resistant to hormone therapy.
It is estimated that 1 in 3 people with castration-resistant prostate cancer who do not develop metastasis will develop bone metastases within 2 years. Once the tumor metastasizes, the prognosis of the patient is extremely poor, and it is basically impossible to survive for 2 years.
Third, the new drug enzaluamine for androgen receptor "love at first sight"
While scientists still don't know how cancer cells continue to grow in the absence of "fuel," they found that androgen receptors are crucial in the process.
Normally, androgen receptors release signals that control the growth and function of the prostate. In patients, androgen receptors can also send signals and instructions to cancer cells to grow. Therefore, as long as this signal transmission process can be cut off, there is hope of inhibiting the development of cancer, and enzaluamine plays such a role.
Enzaluamine is an androgen receptor antagonist, which "falls in love at first sight" on androgen receptors, hugs tightly as soon as it is seen, and does not allow androgens and other molecules to get closer to the receptor, thereby blocking the transmission of cancer cell growth signals.
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So, how effective is enzaluamine in actual combat? Let's take a look at the results of the Phase 3 clinical trial.
Trials of more than 1400 patients with prostate cancer have shown that enzaluamine regimens significantly prolong survival.
Not only that, but the incidence of adverse events in enzaluamine was similar to that of placebo.
The most common adverse effects of Nzaluamine were fatigue and musculoskeletal events; however, the incidence of adverse events leading to death was higher in the enzaluamine group than in the placebo group. The researchers believe that it must be taken into account that the duration of treatment in the enzaluamine group was significantly higher than that in the placebo group (33.9 months vs. 14.2 months).
In the enzaluamine group, the adverse events leading to death were predominantly cardiovascular events, and the incidence was higher than in the placebo group.
Since most patients who died of cardiovascular events had a history of cardiovascular disease, the researchers believe that such deaths should not be related to enzaluamine. However, Gao Xu and Li Jing, urological surgeons at Shanghai Changhai Hospital, believe that the relationship between enzaluamine and cardiovascular-related complications still needs to be paid attention to and further observed by urological surgeons in clinical practice.
Fourth, enzaluamine is listed in China
Currently, Nzaluamine has been approved in the United States for the treatment of patients with non-metastatic castration-resistant prostate cancer. In China, it has also been successfully marketed and approved for the treatment of advanced prostate cancer.
The American Urological Association notes that while innovative prostate cancer drugs are emerging, so far, the impact of each drug on the survival of patients with non-metastatic castration-resistant prostate cancer has been insignificant.
In order to further improve the therapeutic effect, research at this stage must focus on the molecular mechanism of the pathogenesis of castration-resistant prostate cancer and explore the mechanism of drug resistance in order to discover and confirm new and more effective drug candidates.
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