Nobel Laureate in Physiology or Medicine, Gregg L. Semenza, attended the forum
date：2023-09-13 11:35:30 views：
On September 6th, the 6th Belt and Road Forum for Traditional Chinese Medicine Development, as a summit forum of the 2023 China International Fair for Trade in Services, was successfully held at the Beijing National Convention Center. The forum was co-hosted by the National Administration of Traditional Chinese Medicine, the Chinese People's Association for Friendship with Foreign Countries, and the People’s Government of Beijing Municipality, with the theme: 'Deepening Cooperation of Belt and Road Traditional Chinese Medicine Development and Jointly Creating a Global Community of Health for All'. Officials from Chinese and foreign government departments, representatives from international organizations, academicians from the Academy of Engineering, Nobel laureates, and leaders from the political consultative conferences of 10 provinces including Guangdong, Zhejiang, Shaanxi, Yunnan, Jiangxi, Fujian, Sichuan, Gansu, Hebei, and Henan, alongside diplomats from 20 embassies stationed in China from countries such as South Africa, Israel, Belarus, Pakistan, Ethiopia, Zimbabwe, Zambia, Cape Verde, Liberia, Sri Lanka, Uruguay, and Cuba, as well as representatives from over 400 enterprises, participated in the event.
Nobel Laureate in Physiology or Medicine, Gregg L. Semenza, attended the forum and delivered a speech via a prerecorded video
Hello, my name is Greg Semenza. I was the 2019 Nobel Laureate in Physiology or Medicine, and it's an honor for me to address you today. First, I’d like to extend my heartfelt congratulations to the hosts of this event, the National Administration of Traditional Chinese Medicine, the Chinese People’s Association for Friendship with Foreign Countries, and the People’s Government of Beijing Municipality. I wholeheartedly celebrate the successful commencement of the 6th Belt and Road Forum for Traditional Chinese Medicine Development today. The forum serves as a constructive exploration for international collaboration in the realm of traditional Chinese medicine, both domestically and globally. I trust that all esteemed guests present will take this forum as an opportunity for intellectual exchange, building consensus, sharing experience, and business exploration, thereby culminating in tangible collaborative outcomes. Such endeavors significantly contribute to jointly creating a global community of health for all. Through this unique opportunity, I would like to introduce to the distinguished attendees our latest efforts at anti-cancer drug discovery, targeting the Hypoxia-Inducible Factors (HIF).
Well, the hypoxia-inducible factors control physiological and pathological responses to oxygen deprivation. So, in the case of blood loss or anemia, the kidney senses the tissue hypoxia or low oxygen levels and increases red blood cell production through increasing the activity of the hypoxia-inducible factors HIF-1 and HIF-2. However, tumors also consume oxygen resulting in hypoxia within the tumors, which leads to the expression of HIF-1 and HIF-2. And unfortunately, in the context of cancer, HIF-1 and HIF-2 promote cancer progression. Well, there have been the development of drugs that destabilize the HIFs or increase their activity as a treatment for anemia and complementary drugs that inhibit the HIFs for cancer therapy. And I'll be talking about this latter subject for the rest of my remarks. First, some statements about the role of natural products in drug development. About half of all approved drugs over the last 30 years in the U.S. were directly or indirectly derived from natural products. And this also is true for all of the anti-cancer drugs since 1940. About half of them were directly or indirectly derived from natural products. And an example is digoxin, a drug that was used for many years as a treatment for heart disease, which is derived from the Foxglove or Digitalis plant.
And we have been interested in digoxin because we found that it inhibits the accumulation of HIF proteins under hypoxic conditions. And when administered to animals, it has anti-cancer effects. So, in this study, we injected human triple negative breast cancer cells into the mammary pad of immunodeficient mice and treated the mice either with saline control or with digoxin. And you can see that in the animals treated with saline, the tumors grew very rapidly and metastasized to the lymph nodes and to the lungs. Whereas animals treated with digoxin, the primary tumors were significantly inhibited in their growth. The metastasis of cancer cells to the lymph node was significantly reduced and the metastasis to the lungs was completely eliminated by treatment with digoxin to inhibit HIF activity. Unfortunately, digoxin cannot be used in humans at doses necessary for anti-cancer effects because of its cardiac toxicity. Well, we’ve been interested recently in targeting the HIFs in hepatocellular carcinoma, which is the major cause of liver cancer, which in turn is the third leading cause of cancer death worldwide. And it's the most rapidly growing cancer diagnosis in the U.S. It’s been a major problem in Asian countries for many years. Most patients have metastatic spread of the cancer at the time of diagnosis and die within five years. The first approved drugs for metastatic liver cancer provided only several months of increased survival, if at all, with severe side effects and frequent development of resistance.
A new class of drugs that enable the body’s immune system to fight cancer have resulted in dramatic cures of patients with metastatic cancer, but they are effective in less than one-third of the patients who are treated with them. We know that HIF-1 is made at high levels in over half of all human liver cancers and that patients who have high levels of HIF-1 in the initial tumor biopsy are more likely to have a recurrence of liver cancer after surgery or radiation therapy and are more likely to die of liver cancer. HIF-1 plays an important role in enabling cancer cells to evade killing by the immune system and so we wondered could a HIF inhibitor improve the response to immunotherapy in hepatocellular carcinoma. We identified a small molecule that inhibits HIF-1 and HIF-2 that we call 32134D and we found that if we injected liver cancer cells into immunodeficient mice and treated them with saline control, the tumors would grow rapidly. If we treated with a low dose of 32134D, we could significantly inhibit tumor growth and if we used a higher dose, we could inhibit tumor growth to an even greater degree. At the end of the treatment period, we isolated the tumors and analyzed the levels of HIF-1 and HIF-2 and you can see that compared to tumors from animals treated with saline, the animals treated with 32134D had dramatically lower levels of HIF-1 and HIF-2. As far as we could see, the drug had no adverse effects. There was no effect on the body weight, appearance, or behavior of the animals.
When we treated animals that had these liver cancers with immunotherapy, similar to what the patients receive, we could completely eradicate the tumors in 25% of the mice. In contrast, if we treated with a HIF inhibitor, we could eradicate the tumors in 33% of the mice. If we combined the two therapies, we were able to eradicate liver cancer in 67% of the mice that were treated. So, if we could extend this result to the clinic, it would be a dramatic advance in the treatment of liver cancer. And so clinical trials are warranted to test whether this drug is safe and effective in patients with liver cancer. And we hope that those trials will be carried out in the near future. Thank you very much for your very kind attention.