In the 100-year history of cancer research, there are 15 advances and breakthroughs that have proven to be landmark events in the present and future journey of cancer treatment. From radical mastectomy at the beginning of the 20th century, to current precision medicine, to future-proof immunotherapy and molecular-level cancer research, let’s hear it all from Pulse. 1. Cancer: A Systemic Disease In the early 1900s, radical mastectomy was the standard treatment for breast cancer. williamStewartHalsted,theJohnsHopkinssurgeonforeverrememberedforradicalsurgeryforbreastcancer,arguedthatmetastasisoftumorsaftertumorremovalcouldbeattributedtoinadequateoperation.Thesurgeonagreed. The surgeon agreed with that view, performing radical resections for bladder, cervix and kidney cancers. However, seemingly bizarre tumors often reappeared at a distance from the primary tumor. Gradually, the failure of surgery to cure cancer brought back the old concept of cancer as a systemic disease involving body fluids, and therefore called for systemic therapy. 2. Poisons that Cure Since the mid-19th century, scientists have had access to dozens of chemical monomers and compounds, and have worked to find drugs from among them that are powerful enough to kill cancer cells without harming normal cells.In 1947, Sidney Farber, a pathologist at Children’s Hospital in Boston, cured childhood acute lymphoblastic leukemia with aminopterin, a folic acid analog. The result was the first remission of childhood leukemia, thus proving the effectiveness of systemic therapy. 3. Curing tumors became a public health need for the masses? In 1969, there was a lot going on in the United States that deserved to be talked about, from bragging about the moon landing to public protests against the Vietnam War. Very little was said about cancer. That began to change on December 9, when social organizations led by celebrities such as Mary Lasker published full-page ads in the New York Times and the Washington Post. The ad copy quoted Dr. Sidney Farber as saying, “We are so close to curing cancer, we just lack the will and the money and the comprehensive plan like the moon landings.” The public movement against cancer ignited mankind’s war to conquer cancer.In 1971, Richard? President Nixon signed the National Cancer Act, dedicating$1.5 million to cancer research and expanding the responsibilities of the National Cancer Institute. Equally important, the law designated the fight against cancer as a national strategy. 4. Unprecedented Understanding of Cancer At the turn of the 20th century, cancer was thought to be like a black box, with metastases in the brain and various organs being virtually invisible. With the discovery of X-rays, radiation therapy could be used to treat tumors locally, but x-ray images were poorly recognized for soft tissue diseases. This deficiency was ameliorated when Godfrey Hounsfield invented computed tomography (CT) scanning, which was introduced in 1971 to identify patients with suspected brain tumors. This new scanning method allowed physicians to assess the size and location of the tumor and focus on radiation therapy or surgery to target the malignancy, something that could not be done before. 5. Convergence of New Therapies Following the use of single agents to cure childhood leukemia, researchers have evaluated a large number of chemotherapy drugs in different combinations of chemotherapy in an effort to prolong survival for multiple cancers. This research boom resulted in the creation of a number of chemotherapy regimens, BEP, MOPP, CHOP, ABVD. these regimens have yielded encouraging results. Cisplatin (Platinol?) in combination with vincristine (Velban?) and bleomycin (Blenoxane?) (BEP) cured testicular cancer and has become the current standard of care. Adriamycin (Adriamycin?, Doxil?) has been found to be effective against a number of cancers and is now a mainstay of lymphoma treatment as part of the CHOP regimen. Today, adjuvant multidrug chemotherapy has become one of the most important advances in cancer treatment by improving cure rates for breast, colon, lung and other cancers. Risk factors for cancer By 1980, research on cancer-causing factors had made great progress, but few new drugs were actually used in the clinic. The importance of cancer prevention was re-emphasized, and the focus was on smoking cessation. According to official reports from the Department of Health, smoking cessation campaigns and laws prohibiting smoking in public places have led to a steady and sustained decline in smoking in the United States since 1965, and tobacco control and cessation have become one of the most important strategies for reducing the incidence of cancer, especially lung cancer. Research on the link between obesity and cancer prompted the U.S. National Institutes of Health in 1998 published clinical guidelines for the management of obesity, more and more evidence that obesity and cancer are related to enhance the importance of diet and exercise prevention strategies. 7. The benefits of early detection The results of the original breast imaging screening trial showed that imaging screening reduced breast cancer mortality by 40%. Sigmoidoscopy and colonoscopy can be used to detect precancerous polyps and early colorectal cancer, which can often be cured surgically. After being approved by the U.S. Food and Drug Administration (FDA) in 1986, prostate-specific antigen testing became widely used, leading to a surge in the diagnosis of early prostate cancer. Several major cancer screening guidelines have been established, including for breast, prostate, colon, and ovarian cancers.In 2010, cancer screening trials kicked off lung cancer prevention efforts when the U.S. National Lung Cancer Screening Trial demonstrated that low-dose CT scans reduced lung cancer deaths in heavy smokers. Even more exciting is that through continued efforts to improve cancer screening methods, it is expected that cancer can be detected with a simple blood draw test before imaging tests reveal a mass. 8. In local treatment, less is more For some cancers, surgery is a common treatment for the primary tumor, often followed by radiation therapy to control metastasis. In breast cancer, radical mastectomy was the most common treatment until a study published in 1981 showed that restrictive mastectomy was equally effective and reduced the loss of shape. Surgical treatment of prostate cancer, i.e., removal of the prostate, came at the cost of sexual dysfunction and incontinence. Introduced in the early 1970s, brachytherapy pioneered direct radiation to the tumor while preserving normal tissue. Today, minimally invasive laparoscopic surgical treatment allows precise opening of the surgical portal, and more precise radiation therapy techniques have improved the survival and quality of life of many cancer patients. 9. Emphasis on symptom relief Pain is a common symptom in patients with intermediate and advanced cancer, but it is not always managed well. 1986, the World Health Organization issued guidelines to address the use of opioids such as morphine to relieve pain to the satisfaction of patients. The guidelines addressed the concerns of physicians who were reluctant to prescribe this class of drugs given the problems of addiction and abuse. These and many more guidelines for managing symptoms and side effects of treatment better ensure the quality of life for patients at all stages of cancer, and in 2010, the combination of symptom management, or palliative care, and chemotherapy improved survival rates for patients with advanced lung cancer. 10. Individualized Medicine By the late 1970s, HaroldVarmus and J. Michael Bishop developed the genetic theory of carcinogenesis, which suggests that precursors to cancer-causing genes exist in normal cells. The researchers speculated that if precursor genes could be isolated, drugs might be devised to inactivate them. New strategies-targeted therapies-gradually emerged. By 1998, trastuzumab (Herceptin), a monoclonal antibody that interferes with the HER2/neu receptor, was approved, revolutionizing the treatment of patients with HER2-positive breast cancer. 2001 saw the tyrosine kinase inhibitor imatinib (Gleevec?) was approved, also revolutionizing the treatment of patients with chronic granulocytic leukemia. Other targeted therapies followed, launching a new era in cancer treatment. 11. Cancer Genome The Human Genome Project, completed in 2003, has put molecular-based cancer research into overdrive. Over 70 targeted drugs have been approved for lymphoma, leukemia, multiple myeloma, melanoma, breast, lung, prostate, colorectal, pancreatic, liver, cervical, ovarian and other cancers. The goal of the Cancer Genome Atlas is to sequence several types of tumors throughout the genome. Research has uncovered cancer pathways that were not understood 5-10 years ago, thus opening up new possibilities to improve diagnosis, treatment and prevention of cancer. 12. The Emergence of Cancer Vaccines A 1911 report associating viruses with avian rheumatoid sarcoma spurred decades of research confirming the theory of cancer-causing viruses. Gradually, evidence showed a strong correlation between cancer and a number of viral agents, including hepatitis B virus, hepatitis C virus, and human papillomavirus. After numerous efforts, a vaccine against hepatitis B virus was approved in 1981, and in 2006, the FDA approved two vaccines against human papillomavirus types 16 and 18, which account for 70% of all cervical cancer cases. Preparing effective therapeutic vaccines has proven even more difficult. A therapeutic vaccine, Sipuleucel-T (Provenge?), used in some men with metastatic prostate cancer, was approved in 2010. At least 10 types of therapeutic vaccines for cancer are under review. 13. Training of the immune system Can the immune system be trained to weaponize itself against cancer? This question has been on the minds of researchers for years, and tantalizing breakthroughs in metastatic melanoma have given the theory compelling clinical results. in 2011, the FDA approved the use of ipilimumab (Yervoy?), a monoclonal antibody targeting the protein receptor (CTLA4), which can down-regulate the immune system. In 2012, Suzanne Topalian reported on the use of PD-1 antibodies in lung, kidney, and melanoma cancers that resulted in durable remissions. science magazine declared 2013 “the year of breakthroughs” in cancer immunotherapy, “as more and more evidence establishes the field of cancer immunology. 14. Advances in Breakthrough Dimensions Emerging strategies in cancer research look more like science fiction than science. Nanotechnology is developing tiny particles to deliver drugs more directly to cancer cells. Gene expression sequencing assays in which thousands of molecules are measured to obtain a global picture of cellular function can be used to identify cancers from those that are highly aggressive. Proteomics-based technologies can be used to identify biomarkers and protein expression signatures to develop better individualized treatments. Cancer research at the molecular level may bring unprecedented benefits in new dimensions. 15, A Good Sign Two-thirds of patients with invasive cancer now survive for up to five years or longer, up from 49% in 1975. Approximately 14.5 million Americans have been diagnosed with cancer and are still alive today. However, a recent report noted that cancer survivors face physical, financial, educational and personal management issues that last up to 10 years after diagnosis and treatment. Addressing the unmet needs of an unprecedented number of cancer survivors is a serious issue, but a welcome one. The emergence of the cancer survivorship issue itself can be seen as a milestone event in the effort to control this most challenging disease.