In the past, scientists have believed that they know a lot about how cancer affects the body. And they did know a lot about it. However, it is only in the last few years, thanks to major advances in the field of genomics, that they really know anything else about cancer. This knowledge, too, has humbled the scientists. In reality, the way cancer works is more complex than many scientists think. This also raises the question of whether the research paradigm we use to attack cancer needs to be radically improved. The traditional approach to attacking cancer has been for researchers in one field to sell their research in their own narrow field. Joint research by people in multiple fields may be a better research model. “In 2008, a group of researchers, including Spider-Man producer Laura Ziskin (who lost her life to breast cancer in 2011), former Paramount Pictures CEO In 2008, a group of people, including Spider-Man producer Laura Ziskin (who lost her life to breast cancer in 2011) and former Paramount Pictures CEO Sherry Lansing, founded the Fight Cancer Society with the goal of fighting cancer as much as they do film: by bringing together the best and brightest people, funding them, and rigorously monitoring the process. Today, Fight Cancer supports nine interdisciplinary, cross-institutional teams. One of these teams takes advantage of the latest advances in epigenetics, and the teams working on epigenetics include geneticists, pathologists, biostatisticians, biochemists, oncologists, surgeons and nurses. “The team of the Association for the Fight against Cancer evaluates the results of research based on the effectiveness of the treatment of patients, not on published papers. Ambitious plan: According to research data, one in two men and one in three women in some countries will be diagnosed with cancer in their lifetime. Cancer has been called the number one killer of the 21st century and affects us all. How to cure cancer has been a problem that has plagued scientists and doctors for years. Last year, the University of Texas MD Anderson Cancer Center in Houston, the largest cancer research center in the U.S., announced on September 21 its so-called “Moonshot” program, which aims to “significantly improve the survival rate of cancer patients,” officially firing the first shot in the war to end cancer. The first shot was fired in the war to end cancer. Last September, Ronald DePinho, director of MD Anderson Cancer Center, the largest cancer research center in the United States, announced a plan called “Moonshot” to attack cancer with$3 billion over 10 years. De Pinho announced a plan to fight cancer called “Moonshot” DD to significantly improve the survival rate of several cancers over the next 10 years. He said the emergence of ? “a series of game-changing technological advances that will allow us to understand the fundamental basis of the disease. The “moonshot” program, with an estimated investment of$3 billion, plans to “significantly increase survival rates for patients with eight types of cancer” over the next 10 years through six large teams of researchers and clinicians focused on a specific cancer. These eight cancers include acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, melanoma, lung cancer, prostate cancer, triple-negative breast cancer and ovarian cancer. Some researchers have hailed the idea as a way to “overcome cancer” with just one research structure. De Pinho notes that the “moonshot” program will include basic and applied research (such as sequencing tumor genomes), as well as efforts to translate existing knowledge into practice (such as research showing that screening for lung cancer in heavy smokers using a new X-ray imaging technique can save lives). One website describes this goal as “integrating molecular analyses about early and locally advanced lung cancer, which in turn will increase the number of patients cured by 10 to 20 percent.” The project will also include activities related to public awareness to discourage smoking. De Pinhoe compared the program to President Kennedy’s ambitious goal of putting Americans on the moon, announced 50 years ago in the city of Houston. This moon landing analogy is reminiscent of previous goals set for cancer, such as President Nixon’s declaration of war on cancer in 1971. Another example is former National Cancer Institute director Andrew Eisebach’s goal of “eliminating suffering and death from cancer by 2015. Genetic sequencing can detect cancer risks Bree Sandlin, 37, is one of the volunteers in the MD Anderson Cancer Center’s “Moonshot” program. She is a marketing manager for Shell, has twin sons and has triple-negative breast cancer. This is a specific type of breast cancer that is negative for estrogen receptors, progesterone receptors and human epidermal growth factor receptors, for which conventional standard treatment is ineffective, prone to distant metastases and has a poorer prognosis than other types of breast cancer. Currently, Brie is undergoing a trial of methanesulfonic acid treatment with good results. Methanesulfonic acid was approved by the FDA in 2010 for the treatment of patients with recurrent and metastatic breast cancer, and remains controversial. Brie said, “Even if this study doesn’t really cure me, it at least gives me hope.” In addition to the hope that treatment can provide, greater hope comes from the prevention and early diagnosis of cancer. If a patient like Brie has cancer because her genes cause it, do other women in her family have the same disease-causing genes? If family members can test their own genetic profiles, they can find out if they have the same genetic characteristics as Bree, and doctors can save themselves a lot of trouble when diagnosing cancer in its early stages. This is exactly what the “tumor genome sequencing” part of the “moon landing” program is responsible for. There are about 94 million smokers in the United States, and they have a high risk of developing cancer. If they could get a CT scan once a year, they would be able to detect lung shadows and treat lung cancer at an early stage, which could reduce the mortality rate of lung cancer patients by 20 percent. Given that 175,000 new lung cancer patients are diagnosed each year, a 20 percent reduction in mortality could keep tens of thousands of people alive. Blood tests can diagnose and treat cancer, but it’s simply not practical or feasible for so many people to receive a CT scan once a year. So, MD Anderson Cancer Center has recently invented a method to diagnose lung cancer in patients by simply testing their blood for a specific protein profile, combined with diagnostic images and risk models. Using this method, doctors can confirm the diagnosis before the typical symptoms of lung cancer appear. Daniel Haber, director of the Cancer Center at Massachusetts Hospital, led his team in designing the method. Haber led his team to design and develop a microchip covered with 78,000 dots that contain antibodies that bind to cancer cells, which stick to the dots when blood flows through the chip. The test can identify a single cancer cell among more than a billion cells, said Toner, a Harvard University bioengineer who worked on the chip. He added that the team was able to determine this ratio because they mixed the cancer cells into healthy cells and then used the chip to find them. This is like a liquid biopsy,” Harper said, adding that using the chip to examine cancer cells avoids painful biopsy and is more convenient for doctors to use to monitor patients’ conditions than regular imaging scans. This chip has another advantage: after finding out the cancer cells contained in the blood, doctors can prescribe drugs for them, and once a certain drug is determined to be effective on these cancer cells, it can be used on the patient; if the drug or treatment is found to be ineffective after trying, it is not necessary to use it on the patient. This saves medical resources and reduces the suffering of patients in useless treatments. The new method, which is still in the experimental stage, is effective in the diagnosis and treatment of breast cancer, prostate cancer, colon cancer and lung cancer, etc. Currently, four large-scale cancer centers in the United States have begun trials. New Research Professionals Support Interdisciplinary Collaboration Not only cancer treatment research, but also the entire medical community has the disadvantage of being too specific and limited in its research, targeting only a certain symptom or a specific cell, so that the achievements are only small steps at a time. The latest genetic research, which can map the genome of each individual and identify the variants or defects in each individual’s genes, has made scientists realize that previous research methods were one-sided and limited. Various types of cancers such as lung, breast, colorectal and testicular cancers are not separate diseases, but have systemic associations. The same genetic variants can be found in a variety of cancers, such as p53, which controls cell death; a variant condition called BRCA1 is commonly found in a variety of female cancers such as breast and ovarian cancers. In practice, however, breast and ovarian cancers are usually studied by two completely different groups of people who do not communicate with each other. “Such findings make it impossible to separate medicine from science anymore.” According to Dr. Linda Chin of the Institute for Applied Cancer Science at MD Anderson Cancer Research Center (wife of MD Anderson Cancer Center Director Ronald DePinho), “Medicine and science have become tightly intertwined.” In order to conduct holistic research on cancer, it takes not only elite individuals from various specialties and intense research, but also nearly astronomical financial support. In 2008, SU2C was founded with the goal of “fighting cancer” and all of its research projects are overseen by the American Association for Cancer Research. However, the team, from its creation and staffing to its plans and ultimate goals, looked like a Hollywood blockbuster – the most talented people from multiple disciplines, large investments, rigorous planning, tight timelines, and the goal of seeking a big payoff. Through the influence of a few celebrities, SU2C has raised money by launching public service programs on the Internet and television and using the money raised to fund cancer research, raising up to$18 million and a$500,000 grant from the National Institutes of Health. “SU2C’s initial plan was to achieve significant results within three years, and a SU2C committee member would check on the progress of each team every six months. Daniel Hoff, chief scientist at the Virginia Cancer Treatment Center in Arizona, has joined the SU2C “cancer dream team,” and is on the team responsible for tackling pancreatic cancer. He says, “It’s a real challenge to answer people’s questions on a team that has the best of all disciplines and even Nobel laureates.” Dr. Lewis Cantlay of Cornell University Medical College also said, “It’s really exceptional project planning to have to come in every six months to check on progress.” Francis Collins, director of the National Institutes of Health, also strongly supports interdisciplinary research teams: “I am strongly opposed to working alone and strongly support this dream team format of breaking down barriers and bringing together all the different disciplines to work together.” This unique model of group collaboration also breaks down the conventional medical research community. For researchers, their careers are developed, and any data and accolades they receive are shared together; for research institutions, contracts, salaries, titles and intellectual property rights are changed; for pharmaceutical companies, the way new drug trials are conducted needs to be reformed and clinical trials must be regulated. And for patients, it means changes in the way chemotherapy is administered. Research progress has already accelerated dramatically. When the “moon landing” plan was announced, it drew a lot of criticism. Some researchers argued that the project, which treated cancer reduction as an engineering problem, ignored the complexity of the disease and the unpredictability of the science and was rushed. Daniel Harper, director of the Massachusetts Hospital Cancer Center, dismissed the criticism. Previously, he said, people still thought it would be 30 years before they could detect compounds. Scientists do a research project will take eight to 10 years to produce a result, and most of such results on cancer treatment is not groundbreaking, fundamental improvements. But in the “Moon Landing” and “SU2C” projects, scientists can go from discovering a specific variant to inventing a targeted drug in as little as two years. This is the shortest time that can be achieved with the current technology and funding. Even so, Harper still feels that it is not fast enough, “If you are a patient waiting for a life-saving drug, two years is still too long, the cancer cells will not wait for us.” Despite the time constraints, the research paradigm could not be changed overnight. Such interdisciplinary, short-lived research groups face multiple challenges. Because of barriers to communication across disciplines, principal investigators who already enjoy a certain level of prestige take most of the prize money, and the accolades belong to them. As a result, these individuals often seek to retain their positions, which has resulted in many talented young researchers being under-appreciated and under-paid over the past decade or so, which in turn has slowed the development of research standards. The interdisciplinary collaboration in the “Moon Landing” and “SU2C” projects has given young people room to play, and once the results, honors, and prizes are available, they can all share them together, thus attracting many young scholars. This year, a group of technology tycoons, including Facebook founder Mark Zuckerberg and Google co-founder Sergey Brin, joined forces to launch the Breakthrough Prize in Life Sciences, which aims to “reward outstanding research into the treatment of persistent diseases and the extension of human life. The award is designed to “honor outstanding research in the areas of treatment of persistent diseases and human lifespan extension. Dr. Cantlay, one of the first 11 winners, discovered an enzyme called phosphatidylinositol 3-kinase (“PI3K”), an important drug target for new anti-cancer drugs. Cantlay said that PI3K has been shown to be effective in 30 percent of cases in the three major female cancers (ovarian, endometrial and breast). Pharmaceutical companies have been looking for similar compounds to intervene in cancer cells from a biochemical perspective. There are already hundreds of drugs that can have an effect on genetic variants, and while this number sounds like a lot, it also means that the drugs are complex to use. The pharmaceutical industry has a failure rate of up to 95 percent in inventing new drugs, and by the time Phase III clinical trials (i.e., the therapeutic action confirmation phase, which aims to further validate the therapeutic action and safety of the drug in patients with the target indication, evaluate the benefit-risk relationship and ultimately provide a sufficient basis for review of the drug’s registration application) eliminate another half of what remains. “If I find 100 active drug ingredients in the lab and mix them with each other, I can get 10,000 drugs. But we can’t test for all 10,000 drugs.” 1993 Nobel laureate and MIT geneticist and molecular biologist Philip? Sharpe described. But of those 10,000 drugs, how do researchers determine exactly which are suitable for use in patients and which are not? This is one of the major challenges in the development of new drugs. Because PI3K has been shown to be effective in a variety of cancers, Cantlay has organized his own “dream team” to fight cancer. His goal is to start trials as soon as geneticists and biochemists find the right dose. The researchers used PI3K in combination with PARP (a DNA repair enzyme that plays an important role in DNA damage repair and apoptosis and maintains the stability of telomere structure in cancerous cells) against a gene variant called BRCA1, a suppressor gene directly related to hereditary ovarian and breast cancers, and when tested on rats, the BRCA1 gene variant and triple-negative breast cancer were completely cured. This is an unprecedented result. The next stage was human trials. During the previous study, the team needed a PI3K inhibitor from global pharmaceutical giant Novartis and a PARP inhibitor from AstraZeneca Pharmaceuticals, two agents in the experimental phase that had never been used in cancer treatment before, nor had they ever been used in combination. Both companies were wary of this collaboration due to concerns about the intellectual property of the drugs and about their own reputations. By the time Canterrey’s group announced its findings, the situation was immediately reversed, and “every company that makes PI3K inhibitors called me and invited me to work with them.” Canterrey says. The hybrid drug then launched the human trial process at an unprecedented pace, with less than a year from discovery to trial. Canterrey says, “If someone had said they were going to develop a new drug at this pace four years ago, they would have been laughed at by everyone.” New drug makes lung tumors disappear Tom Steinbeck, 62, is a lung cancer patient who has been a smoker for 40 years. Despite having quit smoking, he could no longer breathe or swallow food properly because his lung tumor had grown so large. To stay alive, Steinbeck has gone out of his way to volunteer for new drugs that are still in clinical trials. Some cancers have been shown to be linked to genetic defects or mutations, but doctors and scientists are currently unable to cure cancer patients by altering their genes, so they still have to look for external treatments such as medication. Steinbeck tried a new drug developed by the Johns Hopkins Cancer Research Center that was designed to shrink his tumor. But the Dream Team’s treatment options are far from limited to this drug. The researchers first assumed that the drug would be completely ineffective, but that it would lay a foundation of treatment that would improve the effectiveness of other subsequent treatments. In fact, that’s exactly what Steinbeck experienced. After receiving a round of radiation therapy at the Sloan Kettering Cancer Center in New York, he participated in a second clinical trial. Researchers found that the tumors in his lungs had shrunk significantly compared to when he first entered the trial a year and a half earlier, to the point where they could no longer be scanned with a CT scan. Steinbeck was very happy: “That drug has boosted the activity and utility of T lymphocytes in my body. I’m alive and healthier than I’ve ever been!” Tom Steinbeck is not an isolated case; several other cancer patients who volunteered for the Dream Team study were tested and found to be completely free of their disease. T-lymphocytes are immunologically active human cells that kill cancer cells and are naturally produced in the human body, but in rare quantities. Johns? Hopkins Research Center’s new drug is designed to make the body eliminate tumors on its own by reactivating the patient’s own immune system. In addition to this drug, there are other drugs designed on the principle of cutting off the nutrient supply or blood supply to the tumor cells, or directing the cancer cells to the path of death of normal cells. The latest biotechnology has enabled scientists to identify, label and track specific cancer cells, so several of these treatments have clear targets and their effectiveness will be greatly enhanced. De Pinho says, “Looking back at the project process, you’d be amazed at how fast it went. Yes, it was that fast.” New drug could cure pancreatic cancer Pancreatic cancer is a short-course, fast-progressing, rapidly deteriorating cancer that, once detected, is often too advanced and the vast majority of malignant tumors grow in locations where surgery cannot be performed. Currently, 25 percent of patients with intermediate to advanced pancreatic cancer do not live more than one year after diagnosis. Sharp called pancreatic cancer a “catastrophe”. The goal of the pancreatic cancer group led by Hoff at SU2C is to improve the survival rate of pancreatic cancer patients. The group is made up of 28 academics from five different research institutes. Surgeon Jeffrey Drebin of the University of Pennsylvania Hospital cut a tumor from an already diseased pancreas, which helped the group better understand how the pancreatic cells had changed. When Drebin brought the freshly frozen tumor from the hospital to the University of Pennsylvania lab, two samples were sent to the Gene Expression Laboratory at the Salk Institute and to the Princeton University lab for pancreatic stellate cell analysis and analysis of up to 300 metabolites, including amino acids and sugars. Additional members were analyzed for gene sequencing at Johns Hopkins University and the Translational Genomics Institute. One of the team’s observations is that pancreatic stellate cells may also play a role in the development, progression and metastasis of pancreatic cancer, and may even block the effects of chemotherapy. Tumor cells take nutrients from the rest of the body and supply them to the tumor, which is one of the reasons why pancreatic cancer patients often lose weight so rapidly. If you can block tumor cells from taking up nutrients such as amino acids, perhaps you can make the tumor? “starve” and stop their growth. Also, the team found that vitamin D can help stop changes on the surface of cancer cells that help the body’s own immune system or chemotherapy get inside the cancer cells. Over a two-year period, the team created, evaluated and tested a protein-containing drug that significantly increased the effectiveness of the treatment. 861 patients participated in a phase III clinical trial of the drug while receiving chemotherapy, and the results were promising: 48 percent of the patients were stabilized and no longer progressed after treatment, and the two-year survival rate doubled to 9 percent, with several pancreatic cancer patients even recovering. However, even with the good results, the two-year survival rate of 9% is still a reminder that there is a long way to go in the fight against pancreatic cancer. Problems Collaborative teams are plagued by funding Unfortunately, this interdisciplinary approach is not universally applicable to every type of cancer research, nor can it be applied across disciplines. One of the most basic and simple questions facing these teams today is: How long can interdisciplinary teamwork last? “When SU2C was founded, its founding funds were only enough to sustain the entire team for three years, but some of the teams received additional funding guarantees. The pancreatic cancer team, for example, received two years of funding from the Lustgarten Foundation for Pancreatic Cancer Research and two years of funding from SU2C. At MD Anderson Cancer Center, DePinho supports interdisciplinary teamwork, but he can withdraw funding or replace team leaders he feels are not doing their jobs. Although the state of Texas has allocated$3 billion for such interdisciplinary teams, the money has been hampered by political obstruction and mismanagement. Traditional researchers who struggle in the lab still have a place in such interdisciplinary teams. “Dr. William Nielsen, vice chairman of SU2C and director of the Johns Hopkins Cancer Research Center, said, “The money is not enough to make a difference. Dr. Nielsen says, “There’s no question that we need people who are doing basic research.” Although this is a long-running battle to end cancer, and although researchers have already written a new chapter in the history of this war, there is still more to be written as people learn more about cancer and how it mutates. Everyone is looking forward to a Hollywood-style happy ending.