Professor Guo Jun: Dual-target therapy accurately destroys the power of cancer cell malignancy

In response to the rising incidence and mortality of cancer worldwide, the World Health Organization (WHO) and many oncology-related associations and groups have identified different dates of each year as Disease Care Day for many years, such as February 4 as "World Cancer Day", February 29 as "International Rare Disease Day", April 17 as "World Hemophilia Day", November 17 as "World Lung Cancer Day", etc., calling on countries around the world to continue to carry out scientific publicity, patient education and other activities on these days. To promote the development of cancer prevention and treatment. Melanoma is a malignant tumor with a very high degree of malignancy, the reporter recently interviewed the international well-known expert on melanoma, Professor Guo Jun of Peking University Cancer Hospital on the current progress of melanoma prevention and treatment. Professor Guo Jun used the green-skinned train and the Fuxing high-speed railway as an example to introduce the pathogenesis and clinical scientific research progress of melanoma in a simple and vivid way, bringing promising and good news to melanoma patients.

From black leprosy to tumors: more common in areas where the sun does not shine

Professor Guo Jun told reporters that in simple terms, melanoma is what the people call "black boils", the scientific name is called moles, and it is evil.

But not all "moles" (moles) will turn into melanoma, so you don't have to be nervous. The proportion of nevus turning into melanoma in European and American Caucasians is relatively high, and the incidence of our yellow race is still very low. Melanoma in Caucasia occurs mainly in areas with a lot of sun exposure, such as the back of the chest, face, forearms, lower legs, etc., which is also known as cutaneous melanoma. The most common melanoma in yellow people is not on the skin, but in the fingers, toes, soles and other places that do not grow hair, and have little contact with the sun, which is called melanoma at the end of the limbs (ends of the limbs). Yellow people also have a common type of melanoma, which does not see the sun at all, accounting for about a quarter, which occurs in the nasal cavity, mouth, vagina, colorectum and other parts, we call mucosal melanoma. ”

Professor Guo Jun stressed that melanoma in Caucasians, sunlight is a key causative factor. Ultraviolet rays in sunlight are the culprits of Caucasian disease. Excessive exposure to sunlight leads to genetic variation in mole cells (melanocytes), which, when this mutation accumulates to a certain extent, causes melanoma. Therefore, it is common for Melanoma in European and American Caucasians to have genetic mutations. Nowadays, Europe and the United States emphasize outdoor sun protection in childhood, sun protection at the sea and in the desert, and the elimination of daylight rooms is to prevent ultraviolet excessive exposure to induce melanoma.

From green-skinned trains to high-speed rail: braf v600 gene mutations drive, malignant speed soared

With the deepening of scientific research, the pathogenesis of melanoma has become increasingly clear. Professor Guo Jun introduced, "Although the relationship between melanoma and sunlight exposure in yellow people is not particularly large, and the gene mutation is relatively small, there are still about 25% of the incidence related to genetic mutations, mainly manifested as brafv600 gene mutations, which are the driving genes for the development of melanoma." What are driver genes? It's the genes that drive it forward. In other words, with this mutation, "leprosy" is more likely to turn into melanoma.

Professor Guo Jun especially explained that in the melanoma of Caucasians in Europe and the United States, the braf v600 gene mutation is about 50%-60%, and the Asian melanoma is about 25%. "But if you have this mutation, melanoma develops very fast, in the past we can't do anything about this type of patient, chemotherapy is almost ineffective for braf v600 mutant patients, these patients' disease development rate is almost like a high-speed rail locomotive, and the development rate of melanoma without braf v600 mutation may be a green train."

The State Drug Administration announced in December 2019 that the dual-targeted combination therapy drugs suitable for the treatment of braf v600 mutation-positive non-resectable or metastatic melanoma, dalafenib (trade name teferol) and trimetinib (trade name meginin) have been approved for marketing in China.

When asked about the news of the approval of this dual-target therapeutic drug, Professor Guo Jun said: "Braf v600 mutant melanoma has a high degree of malignancy and rapid development, there was no good way in the past, and now we have a dual-target therapeutic drug like a double-headed missile, and the drive front and rear of this high-speed rail are directly braked, directly hitting its drive system, and all of a sudden this car stops." In the past, the therapy was equivalent to throwing a few wooden sticks on the speeding train tracks to block the train, because the train kinetic energy was huge and fast, this practice could stop it, but it could not stop the cancerous train from continuing to move madly. Professor Guo Jun used a figurative metaphor to explain the advantages of innovative treatment of melanoma.

Professor Guo Jun further succinctly contrasted that chemotherapy is like throwing sleepers on the tracks to block the train's progress, while the newly approved drug is a targeted drug, a precision missile, because it can destroy the pull and thrust of the train from the front and rear ends, forcing the train to stop. It is to completely stop the malignant progression of cancer cells and achieve the purpose of treatment. Professor Guo Jun said excitedly: "This is of great significance"!

It is reported that the results of the study of chinese patients with braf v600 mutation treated with dual-target drugs have confirmed a fairly high efficiency, exceeding 60%, and the progression-free survival time is more than ten months [1], which is basically consistent with the results of dual-target therapy in Caucasian braf v600 mutant patients. Dual-target therapy has shown great power in patients with melanoma with braf v600 mutation in Asia.

Professor Guo Jun also stressed that in addition to single-target and dual-target drugs for the treatment of melanoma, the state has also approved two new immunotherapy drugs: pd-1 monoclonal antibody. But pd-1 monoclonal antibodies work better for melanoma patients who don't have braf mutations.

Looking back on the history of the game with melanoma for decades, Professor Guo Jun sighed with emotion: "Our current treatment methods are colorful, not as helpless as in the past, ten years ago all of our melanoma patients only had one way to chemotherapy, and chemotherapy drugs are one or two, if it is useless, there is no trick at all." In addition to traditional chemotherapy drugs, we have single-target, dual-target, pd-1 monoclonal antibodies, and the survival time of overall melanoma patients is significantly prolonged. In the past, once the melanoma metastasized, the average survival time was half a year, and now 50% of patients with advanced melanoma survive for more than 5 years, which is a huge achievement brought about by scientific progress, and the disease has made a qualitative leap and breakthrough. ”（ [1]kiyohara t,nagano n,miyamoto m,shijimaya t,nakamaru s,makimura k,tanimura h. braf-mutated, acral verrucous melanoma successfully treated by dabrafenib plus trametinib combination therapy. [j]. clinical and experimental dermatology,2019.）

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Text: Liu Ping'an, a reporter for The Health Daily

Editor: Peng Yan

Review: Chen Huiyang, Cao Zheng, Yan Gong