I. Cancer as a systemic disease In the early 20th century, radical mastectomy was the standard of care. William Stewart Halsted, a surgeon at Johns Hopkins Hospital, remembered for radical breast cancer surgery, believed that the spread of the tumor after removal was attributable to the inadequacy of the surgery. Surgeons embraced this concept and adopted radical surgery to treat bladder, cervical and kidney cancers. However, the seemingly mysterious cancers often reappeared in locations far from the primary tumor. The failure of surgical cures for cancer has given way to another old belief that tumors are humoral, systemic diseases that require systemic treatment. The second is the poison that can cure cancer Since the mid-19th century, scientists have been exploring whether a variety of compounds and synthetics have enough ability to kill cancer cells without normal cells being affected by the pool. 1947, Sidney Farber, a pathologist at Boston Children’s Hospital, used the folic acid analogue aminoglycoside to treat acute lymphoblastic leukemia in children, and the treatment made the first time that childhood leukemia The treatment led to the first remission of childhood leukemia and has been accepted as evidence of the concept of systemic therapy. III. A cure for cancer becomes a public need? Americans had a lot to talk about in 1969, from boasting about the moon landing to public protests against the Vietnam War. There was very little talk about cancer. Things did not improve until December 9, when activists led by celebrity Mary Lasker published full-page ads in the New York Times and Washington Post. The ad quoted Dr. Sidney Farber: “We are so close to a cure for cancer, all that is missing is the desire for a cure, money and a plan as well thought out as putting a man on the moon. In 1971 Richard Nixon issued the National Cancer Act, which designated$1.5 million for cancer research and broadened the scope of NCI’s responsibilities. Equally important was the law making the fight against cancer the nation’s top priority. IV. Unprecedented Recognition of Cancer In the early 1900s, cancer was considered a black box, with cancer progressing in the brain and in various tissues and organs, but invisible. With the discovery of X-rays, radiotherapy was used to kill local tumor cells, but X-ray presentation was of limited use in detecting soft tissue disease, a situation changed by Godfrey Hounsfield’s invention of CT. CT scans were introduced into medical practice in 1971 for patients with suspected brain tumors. The new diagnostic tool allowed physicians to assess the size and location of tumors, allowing radiation therapy and surgery to focus on malignant tumors in a way that had never been possible before. V. New treatment options are born The use of single agents to bring childhood leukemia into remission has prompted researchers to evaluate whether chemotherapy in various combinations prolongs survival in multiple cancers. Numerous trials yielded new treatment regimens such as BEP, MOPP, CHOP, and ABVD, and the treatment results were encouraging. Cisplatin combined with Vincristine and Bleomycin (BEP) cured testicular cancer and became the standard of care. Adriamycin was found to be therapeutic for several cancers and, as one of the components of the CHOP regimen, is now the mainstream regimen for the treatment of lymphoma. Today, adjuvant multidrug chemotherapy has increased the cure rate for breast, colon, lung and other cancers, making it one of the most important advances in cancer treatment. VI. Jeopardizing your health By 1980, there were tremendous advances in understanding the occurrence of cancer, but few new drugs were discovered and used clinically, and prevention assumed importance, with smoking being the focus of prevention. Because of the Surgeon General’s report, anti-smoking campaigns and legislation banning smoking in public places were undertaken. Smoking rates in the United States have declined yearly since 1965, and tobacco control and cessation are among the most important strategies for reducing cancer rates, especially lung cancer. Research showing an association between obesity and cancer contributed to the NIH’s 1998 publication of clinical guidelines for managing obesity and anchoring the evidence for obesity-related cancers, emphasizing the importance of diet and exercise as prevention strategies. VII. Early detection benefits The results of the first mammography trial showed a 40 percent reduction in mortality from breast cancer. Sigmoidoscopy and colonoscopy have made it possible to detect precancerous polyps and early colorectal cancer, both of which are often surgically curable. The widely used PSA test, which was approved by the FDA in 1986, has enabled the diagnosis of a large number of early prostate cancers. Screening guidelines have been established for several cancers, including breast, prostate, colon and ovarian cancers. in 2010, the National Lung Cancer Screening Trial showed that low-dose CT reduced deaths from lung cancer in heavy smokers, providing a screening method to initiate cancer prevention. What is more attractive now is the effort to develop new screening methods that can detect cancer through blood tests only before imaging can detect it. Less is more with local treatment Surgery of the primary tumor is a common treatment strategy for several cancers, often followed by radiation therapy to control metastases Radical mastectomy is no longer a popular treatment after studies published in 1981 showed that limited mastectomy was as effective as previous radical excision and less cosmetically disruptive. Surgical removal of prostate cancer comes at the cost of impaired sexual function and urinary incontinence along with the removal of the prostate gland. Brachytherapy, which has existed since the 1970s, is a treatment that directly radiates the tumor area without damaging healthy tissue. Today, less damaging laparoscopic surgery has improved open surgery, and more precise radiotherapy techniques have improved survival and quality of life for many cancer patients. IX. Emphasis on symptom improvement Pain is the most common manifestation of progressive cancer patients, but it has not been well controlled. 1986 WHO issued guidelines on how to use opioids such as morphine to relieve pain to patient satisfaction. The guidelines clarified issues such as addiction and abuse, which at one time discouraged some therapists from prescribing such drugs. Recent guidelines on treating disease symptoms and treating side effects have ensured that patients can have a better quality of life at all stages of cancer. 2010 combined with integrated symptom management or chemotherapy palliative care improved the survival of patients with progressive lung cancer. X. Precision Therapy By the late 1970s, Harold Varmus and J. Michael Bishop developed a genetic theory of cancer development, which implied that precursors of oncogenes existed within normal cells. The researchers hypothesized that if precursor genes could be isolated, drugs could be designed to inactivate these genes. A new therapeutic strategy, targeted therapy, began to emerge, and in 1998 trastuzumab, a monoclonal antibody that interferes with the Her/neu receptor, was approved for marketing, revolutionizing the treatment of HER-2-positive breast cancer patients. Imatinib, a tyrosine kinase inhibitor, was approved in 2001 and has had similarly great success in treating chronic granulocytic leukemia. Other targeted therapeutic agents followed suit, ushering in a new era of cancer treatment. Cancer Genome In 2003, the Human Genome Project was completed, and the research on the molecular mechanism of cancer has entered an accelerated stage. As many as 70+ targeted therapies are used for lymphoma, leukemia, multiple myeloma, melanoma, breast cancer, lung cancer, prostate cancer, colorectal cancer, pancreatic cancer, liver cancer, cervical cancer, ovarian cancer and other cancers. The purpose of cancer genetic mapping is to clarify the complete genome of several tumor types. Research has identified cancer pathways that were not recognized 5-10 years ago, opening up new possibilities for improved diagnosis, treatment and prevention of cancer. XII. The emergence of cancer vaccines After a report in 1911 linking viruses to avian sarcomas, it led to an acceleration of research by decades, confirming the viral theory of cancer occurrence and gradually establishing a strong association between cancer and several viruses, including hepatitis B virus, hepatitis C virus and human papillomavirus. After continuous efforts, the hepatitis B virus vaccine was approved for marketing in 1981, and in 2006 the FDA granted marketing approval for 2 vaccines for human papillomavirus 16 and 18, which are associated with 70% of cervical cancers. The production of an effective therapeutic vaccine has been difficult. sipuleucel-T, a therapeutic vaccine for some men with metastatic prostate cancer, was approved for marketing in 2010. Therapeutic vaccines currently under investigation target at least 10 cancer types. XIII. Training the immune system Can the immune system be armed with training to become a tool to fight cancer? This question has been on researchers’ minds for years when breakthrough clinical trials for the treatment of metastatic melanoma were underway. 2011 saw FDA approval of Ipilinumab, a monoclonal antibody targeting the protein receptor that lowers the immune system (CTLA4). 2012 saw Suzanne Topalian report consistent results with PD-1 antibody therapy in lung, kidney and melanoma. In 2012 Suzanne Topalian reported sustained remissions in lung, kidney and melanoma treated with PD-1 antibodies. Science Magazine claims that cancer immunotherapy made 2013 a breakthrough year with increasing evidence in the field of cancer immunotherapy. Advances in New Frontiers Emerging strategies in cancer research are looking more like science fairy tales than science itself. Nanotechnology is developing small particles to deliver drugs more directly to cancer cells. Gene expression analysis based on the measurement of thousands of molecules depicting overall cellular function is identifying aggressive cancers and less aggressive cancers. Proteomics technologies allow the identification of biochemical markers and protein expression signatures that can be used for individualized therapy. Bringing cancer research to the molecular level will provide unprecedented benefits. XV. A Good Question Two out of three patients with invasive cancers survive 5 years or more, a leap from 49% in 1975. Approximately 14.5 million Americans diagnosed with cancer are still alive today. Recent reports show that cancer survivors face physical, financial, educational and personal control problems that can last up to 10 years after diagnosis and treatment. The unmet needs of such a large number of cancer survivors is a serious issue, but one that we should face with a smile. The emergence of the cancer survivorship field itself can be seen as a milestone in the effort to control one of the most challenging diseases, cancer.