Reference News Network, December 27 report: According to the French magazine "L'Express" website on December 3, in recent years, the means of fighting cancer have been constantly improved, and the cancer death rate has continued to decline. However, cancer remains the leading cause of death in France. Therefore, we need to make further efforts to provide solutions for more patients. Alain Puisieux, who took office as director of the Curie Institute in May 2024, firmly believes that although a "cancer-free world" is out of reach, a "world where all cancers are curable" may be within reach - provided that research investment continues to increase. Below are the main contents of the interview.
Cancer has been with humans for a long time
People often think that cancer is a modern disease. Indeed, the number of cases has doubled in the past 30 years, and the World Health Organization estimates that it will increase by another 75% by 2050. But in fact, since the appearance of multicellular organisms, cancer has existed, because it arises from the inherent defects in cell division and regulation. The best evidence is that we found traces of bone tumors - osteosarcomas - on dinosaur bones, which are almost identical to those suffered by some teenagers today.
Egyptian papyrus documents from around 1500 BC already mentioned "breast tumors" or "breast ulcers," and described the fatal progression. Subsequently, Hippocrates and others in ancient Greece provided the first detailed clinical descriptions, describing tumors as abnormal, incurable, and spreading masses. The concept of "incurability" lasted for a long time, almost until the 19th century when anesthesia appeared. Anesthesia allowed people to consider more complex surgeries to remove certain malignant tumors.
Following the development of radiotherapy (originally derived from Marie Curie's research) and the emergence of the first chemotherapy drugs, the true revolution occurred after World War II. Overall, these methods aimed to attack cells that were proliferating uncontrollably. It was not until the 1970s, especially after 2000, that the mechanisms of tumor development began to be gradually deciphered - first discovering genetic abnormalities in the cancer process, and then gaining a deeper understanding of the immune system's mechanisms. These advances led to the birth of targeted therapies and immunotherapies. Today, we have reached a level where the five-year survival rate is approximately 65%.
What are the innovative therapies?
The website of L'Express Weekly asked: What innovations can take us further in the short term?
Alain Puisieux answered: Various variants of immunotherapy are under development. For example, CAR-T cell therapy, which aims to genetically modify certain immune cells to teach them to specifically attack tumors. There are also bispecific antibodies, which can bring immune cells and cancer cells closer together, allowing the former to destroy the latter.
There are also many innovations in radiation therapy. For example, the "flash radiotherapy" developed by the Curie Institute, which works by delivering a high dose of radiation in an extremely short period. This can kill cancer cells while protecting healthy tissue. Currently, we have a study protocol aimed at developing a prototype to apply this technology to deep-seated tumors.
All these new therapies still share the same goal: to eliminate cells that are over-proliferating. However, we clearly see that this is far from enough, because some cancer cells always manage to adapt to the treatment we apply. It is this "adaptive ability" that leads to recurrence and metastasis, ultimately taking the lives of patients. Take breast cancer as an example: the five-year survival rate for localized tumors can be as high as 95%, but for advanced stages, this figure is less than 35%. This raises the issue of early diagnosis and highlights the need to develop new therapies specifically targeting the tumor's "adaptive ability."
Why is cancer difficult to cure?
Question: How do you define this ability? What exactly does it refer to?
Answer: The traditional view is that cancer is a homogeneous mass of cancer cells, which is completely inconsistent with biological reality. In fact, it is a very heterogeneous ecosystem composed of different types of cells. Cancer cells themselves are extremely diverse: as cells divide, mutations accumulate, and some of these mutations happen to give the cells drug resistance capabilities, leading to recurrence - this genetic heterogeneity is the first major challenge.
But just like everything else in oncology, tumor heterogeneity has another dimension, which we call cellular plasticity. This process is unrelated to genes: even without new mutations, cancer cells can "change shape" to adapt to external pressure. I often use the analogy of "Barbie" - those cartoon characters that change shape and color at will for their children. The problem is that after each transformation, cancer cells gradually acquire increasingly invasive characteristics, including the ability to form metastases.
The metastasis process is extremely complex, but fortunately, not all cancer cells can take this path: the cells must be able to break away from the primary tumor, carve a path through adjacent tissues, enter the bloodstream, survive in the blood flow, exit the blood vessels, adapt to the new tissue to form new tumors. Most cells die at one of these steps, but a few survivors can reignite the fire far from the original site.
Currently, whether it is chemotherapy, radiotherapy, targeted drugs, or indirect immunotherapy, in the end, they are all attacking the "proliferation ability" of the tumor. If we want to take a step further, we must find ways to prevent cancer cells from "randomly adapting" - I believe this is their real致命 threat.
How should we respond?
Question: Then, what should we do?
Answer: We must understand the underlying mechanisms as thoroughly as possible. For example, in our team, researchers found that metastatic cells "appropriate" iron and copper to help them adapt to the new environment.
At the same time, prevention policies are crucial. It is estimated that 40% of cancers are preventable. When asking French people about the impact of smoking, they usually answer that one out of ten smokers will die from smoking. Actually, it's one out of two - it really needs to be recognized! In addition, there are the effects of alcohol, sedentary lifestyle, and obesity. We must also improve the quality of screening and early diagnosis so that we can detect tumors when they are still curable.
Question: What are the paths for progress? Can we really detect tumors at an extremely early stage using blood?
Answer: I look forward to that day, but I must be honest: when it comes to large-scale screening for the general population, we haven't reached that point yet. Companies have already launched "a tube of blood to check 100 cancers" packages, but at this stage, they are more likely to cause unnecessary anxiety and over-testing. However, circulating tumor DNA (ctDNA) technology has already been able to assess the effectiveness in clinical settings in real-time and detect signs of recurrence earlier, which is a practical application that can benefit patients today.
The next step in prevention is "precision prevention." Everyone's exposure history, genetic background, and lifestyle differ, and we need to identify the highest-risk subgroups, customize screening programs and follow-up schedules for individuals, and use radiomics and artificial intelligence (AI) to detect lesions as early as possible.
Question: What else can AI help with?
Answer: AI can also play a big role in other areas. With the explosive growth of treatment options, the dilemma doctors face is: how to find the right person, grasp the right time, and use the right combination. We need predictive biomarkers to identify "responders" and "non-responders" in advance. AI can mine features from massive patient data to help us find the best drug combinations, achieving a "multi-target, low-toxicity" collaborative blockade, thus making it impossible for tumors to adapt and escape. (Translated by Pan Geping)
Original: toutiao.com/article/7588434287884648969/
Statement: This article represents the views of the author alone.