Author: NEJM Frontiers in Medicine
Which is the only organ in the male body that maintains lifelong growth?
The answer is, the prostate.
Its growth process is sometimes fast and sometimes slow, growing rapidly in adolescence, and entering the “second spring” in middle-aged and old age. In some middle-aged and elderly men, it grows too large and becomes what is commonly referred to as benign prostatic hyperplasia. However, an overgrown prostate is not life-threatening.
1. Prostate cancer: the sixth most common malignant tumor in men
In contrast, prostate cancer is a malignant cell proliferation that ranks first in the incidence of male malignant tumors in Europe and the United States for many years.
Although the incidence of prostate cancer in my country is lower than that in European and American countries, prostate cancer is becoming more and more common due to the aging of the population, the increase in diagnosis rates and changes in lifestyle in recent years. According to the 2015 China Cancer Annual Report, prostate cancer ranks sixth in the incidence of male malignant tumors.
Currently, the main treatment for prostate cancer is to inhibit the androgen secreted by the patient’s body, but the sustainability is not strong, and the tumor is prone to develop into “castration-resistant prostate cancer”, that is, resistance to hormone therapy.
Researchers have developed a new therapy that disables cancer cell signaling by controlling the androgen receptor. Recently, the top international journal “New England Journal of Medicine” published the results of the Phase 3 clinical trial of enzalutamide.
As one of the representative drugs of new therapy, what is its clinical effect?
Image source: Zhanku Hailuo
Second, Buffett, Murdoch are all beneficiaries: suppress androgen, stop “fuel” supply
Although the pathogenesis of prostate cancer is flawed and punished
In 1941, American surgeon Charles Brenton Huggins and others discovered that surgical removal of the testicles to suppress androgen production, or estrogen supplementation to block androgen receptors, was extremely effective in suppressing androgen production. Effectively control 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 act as “fuel” for cancer cells – as long as the fuel supply stops, prostate cancer cannot continue.
Charles Brenton Huggins was awarded the 1966 Nobel Prize in Physiology or Medicine for this important discovery, which later became known as “androgen deprive therapy” , ADT), and has long been the treatment of choice for prostate cancer. It has helped most patients truly achieve “survival with tumors” or “coexistence with tumors”, and Buffett, the stock god, and Murdoch, the media tycoon, are all beneficiaries.
Unfortunately, in some cancer patients, androgen deprivation therapy only results in remission of prostate cancer for 2-3 years. This is because the cunning cancer cells have gradually found countermeasures and can still make waves without “fuel”. The disease inevitably progresses to “castration-resistant prostate cancer,” that is, resistance to hormone therapy.
It is estimated that 1 in 3 men with castration-resistant prostate cancer without metastases will develop bone metastases within 2 years. Once the tumor metastasizes, the prognosis of the patient is extremely poor, basically unable to survive for 2 years.
Image source: Zhanku Hailuo
Three, the new drug enzalutamide “love at first sight” for androgen receptor
While scientists still don’t know how cancer cells continue to grow without “fuel,” they have discovered that the androgen receptor is crucial in the process.
Normally, the androgen receptor sends signals that control the growth and function of the prostate. In patients, androgen receptors also signal and instruct cancer cells to grow. So, as long as this signaling process can be cut off, there is hope for inhibiting cancer development, and enzalutamide plays that role.
Enzalutamide is an androgen receptor antagonist. It “loves at first sight” for the androgen receptor, and hugs it tightly as soon as it sees it, preventing molecules such as androgens from being released. It gets closer to the receptor, thereby blocking the transmission of cancer cell growth signals.
Image source: Tencent Medical Dictionary
So, how does enzalutamide work in practice? Let’s take a look at the results of the Phase 3 clinical trial.
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Trials of more than 1,400 men with prostate cancer show that the enzalutamide regimen significantly prolongs survival.
Not only that, but enzalutamide had a similar rate of adverse events compared to placebo.
The most common adverse effects of enzalutamide were fatigue and musculoskeletal events; however, the rate of adverse events leading to death was higher in the enzalutamide group than in the placebo group. The investigators concluded that treatment duration in the enzalutamide group was significantly longer than in the placebo group (33.9 months vs. 14.2 months).
In the enzalutamide group, the major adverse events leading to death were cardiovascular events at a higher rate than in the placebo group.
Since most of the patients who died of cardiovascular events had a history of cardiovascular disease, the investigators believe that these deaths should not be related to enzalutamide. However, Gao Xu and Li Jing, urologists of Shanghai Changhai Hospital, believe that the relationship between enzalutamide and cardiovascular-related complications still needs to be paid attention and further observed by urologists in clinical practice.
IV. Enzalutamide is listed in China
Enzalutamide is currently 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 points out that despite the emergence of innovative prostate cancer drugs, the impact of each drug on the survival of patients with non-metastatic castration-resistant prostate cancer has so far been negligible. of.
In order to further improve the therapeutic effect, the current research must focus on the molecular mechanism of castration-resistant prostate cancer, and explore the drug resistance mechanism in order to discover and confirm new and more effective drug candidates .
Image source: Zhanku Hailuo
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