The Journey of Human Fight Against Cancer in 250 Years

Cancer, as a disease, has been recognized by mankind for thousands of years. In the past 250 years, we have witnessed a series of milestones in the fight against cancer. Here, we list some key milestones in the field of cancer research.

1775: Chimney Smoke and Squamous Cell Carcinoma

Percivall Pott linked chimney smoke exposure to scrotal squamous cell carcinoma of the chimney sweeper. He was the first person to report a clear relationship between environmental exposure and cancer.

1863: Inflammation and Cancer

Rudolph Virchow identified white blood cells in cancer tissue, linking inflammation to cancer for the first time. He coined the term [leukemia] to describe the excess of white blood cells in patients with the disease.

1882: First radical operation for breast cancer

William Halsted performed the first radical surgery for breast cancer. Until the second half of the 20th century, this surgical method was still the standard surgical method for breast cancer treatment.

1895: First X-ray

Wilhelm Roentgen discovered X-rays. The first X-ray was his wife’s hand.

1898: Radium and polonium

Marie Curie and Pierre Curie discovered radioactive substances-radium and polonium. A few years later, radium was used in cancer treatment.

1902: Cancer and Single Cell Chromosome Damage

Theodor Boveri proposed that cancer comes from a single cell with chromosome damage, believing that chromosome changes lead to runaway cell division.

1903: The First Application of Radiotherapy in Cancer Treatment

S.W. Goldberg and Efim London used radium to treat two patients with basal cell carcinoma of the skin. Both patients were cured of cancer.

1909: Immune Surveillance

Paul Ehrlich proposed that the immune system can inhibit the formation of tumors, which was then called the [immune surveillance] hypothesis. Now this hypothesis has become a proven theory and is still guiding the current cancer research to use the power of the immune system to fight cancer.

1911: Cancer in Domestic Chickens

Peyton Rous discovered a virus (Lloyd’s sarcoma virus) that can cause cancer in domestic chickens, confirming that some cancers are caused by infectious factors.

1915: Cancer in Rabbits

Katsusaburo Yamagiwa and Koichi Ichakawa found that when coal acts on rabbit skin, it can induce cancer in rabbits. For the first time, they provided experimental evidence that chemicals can cause cancer.

1928: Pap smear

George Papanicolaou discovered that cervical cancer can be screened by microscopic examination of cells in the vagina. This breakthrough led to Pap smear examination. The examination can find abnormal cervical cells and eradicate them before they become cancerous.

1932: Modified radical mastectomy

David H. Patey developed modified radical mastectomy, which was less destructive to the patient’s body than radical mastectomy and eventually replaced it as the standard procedure for the treatment of breast cancer.

1937: National Cancer Institute (NCI)

U.S. President Franklin D. Roosevelt signed a law to establish the National Cancer Institute (NCI).

1937: Breast-conserving surgery and subsequent radiotherapy

George Keynes described a new treatment for breast cancer: breast-preserving surgery followed by radiotherapy on the premise of complete tumor resection. After the tumor is removed by surgery, a long needle containing radium is inserted into the affected breast and the axillary lymph node area adjacent to the same side.

1941: Hormone therapy

Charles Huggins found that removing testicles to reduce testosterone production or regulate estrogen levels can cause prostate tumors to subside. Artificial regulation of this hormone is known as hormone therapy. It is still one of the main treatments for prostate cancer.

1947: Antimetabolites

Sidney Farber demonstrated the therapy of antimetabolic drug aminopterin (a folic acid derivative), which can promote temporary remission of acute leukemia in children. The structure of antimetabolic drugs is similar to that of chemicals needed in important physiological processes in cancer cells, such as DNA synthesis, and can induce cancer cell death by blocking these processes.

1949: Nitrogen mustard

The Food and Drug Administration (FDA) agrees that nitrogen mustard is used to treat cancer. Nitrogen mustard belongs to a class of drugs called [alkylating agents]. Alkylating agents can kill cancer cells by chemically changing DNA.

1950: Smoking and Lung Cancer

Ernst Wynder, Evarts Graham and Richard Doll demonstrated that smoking is one of the main factors inducing lung cancer.

1953: The first complete cure of human solid tumors

Roy Hertz and Min Chiu Li used chemotherapy for the first time to cure solid tumors. The specific situation is that they used the chemotherapy drug methotrexate to treat villous cell carcinoma. Villous cell carcinoma is a rare malignant tumor of reproductive histiocyte that mainly affects women.

1958: Combined chemotherapy

Experts Emil Frei, James Holland and their team from the National Cancer Institute (NCI) showed that the combined chemotherapy of 6-mercaptopurine and methotrexate can partially or completely relieve acute leukemia in children and adults and prolong the survival time of patients.

1960: Philadelphia Chromosome

Peter Nowell and David Hungerford described a common chromosome in cancer cells of patients with chronic myeloid leukemia. This chromosome is called [Philadelphia chromosome] and exists in 95% of chronic myeloid leukemia.

1964: Attention to Smoking

The U.S. Department of Health has issued a report stating that smoking is a major health threat in the United States and actions are needed to reduce the harm of smoking.

1964: EB virus

For the first time, the virus (EB virus) was linked to human cancer (Burkitt’s lymphoma). EB virus was later found to induce several other cancers, including nasopharyngeal carcinoma, Hodgkin’s lymphoma and some gastric cancers.

1971: National Cancer Act

On December 23, President Richard M. Nixon signed the National Cancer Act, which authorizes the head of the NCI to coordinate all activities of the National Cancer Program, establish the National Cancer Research Center, and establish the National Cancer Control Program.

1976: Proto-oncogene

Dominique Stehelin, Harold Varmus, J. Michael Bishop and Peter Vogt discovered a gene in normal domestic chicken cells related to the oncogene of poultry sarcoma virus, which can cause cancer in domestic chickens. This eventually led to the discovery of human proto-oncogene.

1978: tamoxifen

The FDA approved tamoxifen (an anti-estrogen drug originally used as contraception) to treat breast cancer. Tamoxifen is the first generation of selective estrogen receptor modulators (SERMs) approved for anti-cancer.

1979: TP53 gene

TP53 gene, also known as p53, is the most common mutant gene in human cancer and was discovered in 1979. It is a tumor suppressor gene, meaning that the protein it encodes (p53 protein) can control cell proliferation and inhibit tumor growth.

1984: Human papillomavirus 16 and 18

Scientists have detected genes of human papillomavirus (HPV) subtypes 16 and 18 from most cervical cancers, thus establishing a clear relationship between HPV subtype infection and cervical cancer.

1985: Breast-conserving surgery

The results of an NCI-supported clinical trial show that breast-conserving surgery (breast mass resection) + postoperative total breast radiotherapy for early breast cancer patients have similar overall survival rate and tumor-free survival rate compared with breast cancer patients undergoing total mastectomy alone.

1986: Cloning of HER2 Proto-oncogene

Human proto-oncogene HER2 (also known as Neu gene and Erbb2 gene) has been cloned. Overexpression of protein products encoded by this gene occurs in 20%-25% of breast cancer patients (HER2 positive breast cancer), which is related to strong invasiveness of the disease and poor prognosis.

1993: Guaiac fecal occult blood test (FOBT)

An NCI-supported clinical trial showed that anal finger diagnosis combined with fecal occult blood test (FOBT) can effectively reduce colon cancer mortality by 33%. (Guaiac is a test reagent-editor’s note)

1994: Cloning of BRCA1 tumor suppressor gene

The tumor suppressor gene BRCA1 has been cloned. The special genetic mutation of this gene can increase the risk of breast cancer and ovarian cancer in women, as well as several other common cancers in men and women.

1995: Cloning of BRCA2 tumor suppressor gene

The tumor suppressor gene BRCA2 has been cloned. Similar to BRCA1, the gene’s special hereditary BRCA2 variation can significantly increase the risk of breast cancer and ovarian cancer in women, as well as several other common cancers in men and women.

1996: anastrozole

The FDA has approved anastrozole for the treatment of estrogen receptor-positive advanced breast cancer in menopausal women. Anastrozole is the first aromatase inhibitor approved for cancer treatment. The drug blocks the production of estrogen in the body.

1997: rituximab

FDA approved rituximab (a monoclonal antibody) for the treatment of drug-resistant, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL). Rituximab was soon approved for initial treatment of some types of non-Hodgkin’s lymphoma, including diffuse large B-cell lymphoma and chronic lymphoblastic leukemia.

1998: NCI funded breast cancer prevention trials

The NCI-funded breast cancer prevention trial shows that the anti-estrogen drug tamoxifen can reduce the incidence of breast cancer in some high-risk women by up to 50%. The Food and Drug Administration approved tamoxifen to reduce the risk of breast cancer in high-risk women.

1998: Trastuzumab

The FDA approved trastuzumab (another monoclonal antibody) for the treatment of HER2-positive metastatic breast cancer in women. The monoclonal antibody targets cancer cells that overexpress HER2 protein. Trastuzumab was soon approved for adjuvant (postoperative) treatment of HER2-positive early breast cancer in women.

2001: imatinib mesylate

A clinical trial showed that imatinib mesylate is effective in the treatment of chronic myeloid leukemia. Imatinib mesylate targets a unique protein encoded by [Philadelphia chromosome]. Later, it was considered effective in the treatment of gastrointestinal stromal tumors (GIST).

2003: NCI-funded Prostate Cancer Prevention Trial (PCPT)

The NCI-funded Prostate Cancer Prevention Test (PCPT) results show that finasteride can reduce the risk of prostate cancer by 25%. The drug works by reducing the production of androgen in the body.

2006: NCI Tamoxifen, Raloxifen Study (STAR)

NCI tamoxifen and raloxifene study (STAR) results show that if menopausal women with high risk of breast cancer take anti-estrogen drug raloxifene, their risk of onset can be reduced. The risk of serious side effects of raloxifene is lower than that of tamoxifen.

2006: Cervical cancer vaccine Gardasil

The FDA approved the human papillomavirus (HPV) vaccine Gardasil to prevent cervical cancer. The vaccine targets two subtypes of HPV, which can cause 70% of cervical cancer. NCI scientists have developed the basic technology for making Gardasil.

2009: Cervarix vaccine for cervical cancer

The FDA approved Cervarix to prevent cervical cancer. This is the second cervical cancer vaccine that protects women from two subtypes of human papillomavirus (HPV). These subtypes cause about 70% of cervical cancer. NCI scientists have developed the basic technology for making Cervarix.

2010: The first therapeutic human cancer vaccine sipuleucel-T

The FDA approved sipuleucel-T for treatment of metastatic prostate cancer that has failed hormone therapy. The vaccine can use the patient’s own immune system cells (dendritic cells) against cancer cells. The vaccine is the first and only therapeutic cancer vaccine to date.

2010: NCI Funded Lung Cancer Screening Test (NLST)

Preliminary results of the NCI-funded Lung Cancer Screening Test (NLST) show that low-dose spiral CT can reduce lung cancer mortality by 20%. The screening is mainly aimed at a large group of heavy smokers who have not quit smoking or have quit smoking.

2011: Ipilimumab

The FDA approves Ipilimumab (a monoclonal antibody) for the treatment of inoperable or metastatic melanoma. Ipilimumab activates the immune system to attack cancer cells by removing the brakes that control the intensity of the immune response.

2012: NCI-funded PLCO Cancer Screening Test

The results of the NCI-funded PLCO cancer screening test show that using soft sigmoidoscopy to screen colon cancer in people over 55 years old can reduce the incidence and mortality of colon cancer. In the PLCO test, the screened population reduced the risk of colon cancer by 21% and the mortality rate of colon cancer by 26% compared with the control group.

2013: Ado-Trastuzumab Emtansine (T-DM1)

The FDA has approved Ado-Trastuzumab Emtansine (T-DM1) for the treatment of HER2-positive breast cancer patients who have previously been treated with trastuzumab and/or taxanes. T-DM1 is an immunotoxic drug (antibody-drug conjugate), specifically linking the monoclonal antibody trastuzumab to the cytotoxic substance mertansine, which can inhibit cell proliferation by blocking microtubule formation.

2014: Cancer DNA Analysis

Researchers from the Cancer Genome Map (TCGA) program, In cooperation with the NCI and the National Human Genome Research Institute, Analysis of DNA and other molecular changes in more than 30 human cancers. They are based on distinguishing different characteristics of tumors. It is found that gastric cancer is actually a category 4 disease, not a category 1. TCGA’s discovery and other related plans may lead to a new classification system for cancer production. The classification system is based on different molecular abnormalities of tumors, combined with organs or tissues at the primary site.

2014: Pembrolizumab

The FDA approved Pembrolizumab for use in the treatment of advanced melanoma. This monoclonal antibody blocks the action of a protein called PD1, which exists in immune cells, thus enhancing the immune system’s ability to fight cancer.

The journey is far from over, and the dawn of human conquest of cancer has appeared…

Responsible Editor: Ding Ruoshui

This article is translated from the National Cancer Institute of the United States. The translator exclusively authorizes Clove Garden to use it and refuses to reproduce it in any other form.