Timeline

And MSU's impact on cancer

2010 - 2019

2019 – FDA approved pembrolizumab for the adjuvant treatment of patients with melanoma, stage III non-small cell lung cancer, advanced renal cell carcinoma, head and neck squamous cell carcinoma, metastatic small cell lung cancer, advanced esophageal squamous cell cancer, and more.
2019 – Michigan State University opens the Interdisciplinary Science and Technology Building to bolster the university’s commitment to providing interdisciplinary research space to support significant growth in STEM-related fields: science, technology, engineering, and mathematics.
2017 – Michigan State University celebrates the opening of the new MSU Grand Rapids Research Center for medical researchers and scientists studying human health, and the Institute for Quantitative Health Science & Engineering (IQ) building, dedicated to basic and applied research at the intersection of engineering, human medicine, and natural science.
2015 – NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trials open for enrollment. This phase II precision medicine trial explores treating patients based on the molecular profiles of their tumors regardless of cancer type.
2014 – The FDA approves olaparib for advanced ovarian cancer along with a laboratory-developed test (LDT) companion diagnostic to identify appropriate patients through the detection of the presence of mutations in BRCA genes in blood samples. Olaparib is the first FDA-approved therapeutic that inhibits PARP and was approved with the genetic test, BRACAnalysis CDx, a companion diagnostic.
2014 – After more than five years of design and preliminary construction activities, work officially begun on the construction for the Facility for Rare Isotope Beams (FRIB). The FRIB at Michigan State University will open in 2022 as a scientific user facility for the Office of Nuclear Physics in the U.S. Department of Energy. The FRIB will enable scientists to make discoveries about the properties of rare isotopes (that is, short-lived nuclei not normally found on Earth), nuclear astrophysics, fundamental interactions, and applications for society, including in medicine and cancer.
2012 – Major immune checkpoint inhibitor shows dramatic clinical trial results. An anti-PD-1 monoclonal antibody drastically shrank tumors in patients with melanoma, kidney cancer, and advanced non-small cell lung cancer.
2011 – BRAF inhibitor vemurafenib and its companion diagnostic are approved by the FDA to treat melanoma tumors expressing the BRAF V600E mutation. BRAF is mutated in approximately half of those with late-stage melanoma.

2000 - 2010

2008 – The U.S. Department of Energy selects Michigan State University to design and establish the Facility for Rare Isotope Beams, a $730 million facility that will advance understanding of rare nuclear isotopes and the evolution of the cosmos. More…
2008 – DNA sequencing of a human cancer, acute myeloid leukemia, is reported.
2006 – The Cancer Genome Atlas is established to map cancer genes. The Cancer Genome Atlas (TCGA), a collaboration between the National Cancer Institute and the National Human Genome Research Institute, seeks to identify the changes in each cancer’s complete set of DNA.
2004 – Vaccines against human papillomavirus (HPV) are developed to prevent cervical cancer. Vaccination against the most common oncogenic human papillomavirus types, HPV 16 and HPV 18, could prevent up to 70% of cervical cancer cases worldwide.
2002 – The third derivative of cisplatin, oxaliplatin, was FDA approved for metastatic colorectal cancer in combination.
2001 – Two ligands for inhibitory PD-1 are identified. Engagement of PD-1 by either of its two newly discovered ligands (PD-L1 and PD-L2) drastically inhibits T cell receptor-mediated proliferation and cytokine production. This pathway will become a major target for cancer immunotherapy.
2001 – Draft sequence of the human genome is published. A public, free-access, complete human genomic sequence allows researchers to perform many experiments, including but not limited to studies of comparison with other organisms, predictions of gene functions, identification of new genes involved in cancer, and design of new diagnostics and therapeutics.

1990 - 2000

1998 – Positron emission tomography (PET) scanner is approved for functional imaging. PET uses an injected dye to view tissues that are highly metabolically active. PET can identify tumors that are fast growing and active.
1998 – Use of a monoclonal antibody (trastuzumab, Herceptin) significantly improves survival in advanced Her-2/neu breast cancer.
1997 – Rituximab (Rituxan) approved by the FDA for the treatment of B-cell non-Hodgkin lymphoma resistant to other treatments. Rituximab was the first monoclonal antibody FDA approved for the treatment of cancer.
1995 – Computer-guided technology improves delivery of radiation therapy. Computerized systems improve the accuracy of radiation therapy with better focusing on the tumor, reducing damage to surrounding healthy tissue.
1990 – NIH and the U.S. Department of Energy formally begin the Human Genome Project. BRCA1 mutations are associated with breast cancer.

1980 - 1990

1989 – The second derivative of cisplatin, carboplatin, was FDA approved for advanced ovarian cancer.
1987 – The receptor, Her-2/neu, is found to be overexpressed in some breast cancers.
1986 – Retinoblastoma gene, RB, is identified. The retinoblastoma gene, RB, was identified in children with hereditary retinoblastoma and shown to be a tumor suppressor gene.
1983 – Oncogene cooperation for malignant transformation is demonstrated. The observations that normal cells required multiple genetic events to become transformed provided a model for the molecular basis for the multistep nature of cancer.
1983 – Human papillomavirus is identified as the causative agent of cervical cancer.

1970- 1980

1978 – FDA approves Cisplatin for use in cancer (testicular, ovarian and bladder cancers).
1977 – DNA sequencing is developed. RNA splicing is demonstrated. Medical magnetic resonance imager (MRI) scanner is developed. Tamoxifen is approved for treatment of breast cancer.
1974 – DNA cloning methods are developed. The ability to clone DNA was the basis for determining the sequence of the human and other genomes.
1974 – First Lady Betty Ford undergoes a mastectomy and speaks publicly about breast cancer.
1971 – President Richard Nixon declares “War on Cancer” in State of the Union Address and signs the National Cancer Act.
1971 – Two-hit hypothesis is proposed. Using retinoblastoma as a model and observing patients with one or both eyes affected and those with and without a family history of disease, it was shown how cancer can be caused by two mutational events.
1971 – Taxol, a natural plant product, is developed for chemotherapy. A component of the Pacific yew tree, taxol was shown to actively inhibit leukemia cell lines in vitro.

1960 - 1970

1969 – Rhabdomyosarcoma is an inherited familial cancer syndrome. A study of children with rhabdomyosarcoma who had relatives who developed other organ-site cancers at an early age led to the identification of a familial cancer syndrome, later shown to be primarily influenced by inherited mutations in p53.
1967 – Estrogen receptor is identified. Targets in uterine tissue were identified that interact specifically with estrogen. This finding was the first step that led to the detection of estrogen receptors in breast cancers and the design of specific and effective therapies for hormone-dependent breast cancer.
1965 – Chemistry professor Barnett Rosenberg and colleagues Loretta VanCamp and Thomas Krigas observe that certain platinum compounds inhibited cell division, and by 1969 demonstrate that these compounds cured solid tumors. More…
1964 – RAS is identified. Research on RAS began with the first observation that a preparation of a murine leukemia virus isolated from a leukemic rat induced sarcomas in newborn rodents.
1960 – Growth factors are purified and identified. The fact that growth factors were necessary for cells to survive and replicate had long been known, but the individual components of serum responsible had not been identified.
1960 – The Philadelphia chromosome is discovered. An abnormally small chromosome was identified in the neoplastic cells of patients with chronic myelogenous leukemia. This small chromosome, later named the Philadelphia chromosome after the city in which it was discovered.
1960 – American Cancer Society urges widespread use of Pap smear to detect cervical and uterine cancers. Screening techniques for prevention of colon cancer are adopted.

1950 - 1960

1953 – Human carcinoma cell line, HeLa, is established. The HeLa epithelial cell line is readily grown in laboratories worldwide and has become a fundamental tool for studying many aspects of molecular biology.
1953 – Structure of DNA is described. Not only was the global structure of DNA identified, but how the bases pair and possible implications for methods of replication were also elucidated.
1951 – Ultrasound imaging is developed for detecting tumors. Although earlier studies had used ultrasound as a therapy and had examined its use as an imaging tool, research showed that ultrasound could detect differences in density between malignant and normal tissues.
1950 – Epidemiologic work links tobacco smoking to lung cancer. A retrospective analysis of the smoking habits of patients with lung cancer showed an association with tobacco. This was followed by a prospective study of male doctors that showed a clear relationship between smoking and lung cancer deaths. Tobacco exposure is now a known risk factor for many cancer types, accounting for an estimated 30% of all cancer mortality.

1940 - 1950

1948 – First successful chemotherapy for childhood leukemia is reported. A synthetic folate antagonist achieved a 3-month remission in 10 of 16 children with leukemia. Although not successful by today’s standards, this was an important result that would lead to further work on antimetabolites and the first generation of effective chemotherapeutic agents.
1946 – Nitrogen mustard is established as the first chemotherapeutic agent. Observational reports that soldiers exposed to nitrogen mustard during wartime had low white blood cell counts led to the testing of nitrogen mustard as chemotherapy for cancer. Intravenous nitrogen mustard was shown to slow the growth of lymphomas and leukemias in patients refractory to radiation therapy, and it achieved remissions of a few months. Nitrogen mustard was approved for cancer treatment in 1949.

1930 - 1940

1939 – Transplanted animal tumors are shown to grow blood vessels. Tumors transplanted into the ears of rabbits elicited a vascular network. This was early evidence of the phenomenon of angiogenesis, or new blood vessel growth, which would later become a target for anti-angiogenesis cancer therapies.
1937 – President Franklin D. Roosevelt signs the National Cancer Institute Act establishes the National Cancer Institute (NCI).

1920 - 1930

1930 – The first pure carcinogen, benzopyrene, is isolated from coal tar. The known cancer-causing environmental substance, coal tar, was fractionated into components and assayed in mouse models to identify the individual chemicals responsible for carcinogenesis.
1928 – Cervical cancer cells are visible in smears of exfoliated vaginal cells. Findings of cervical cancer cells in smears were met with skepticism, and it would take until the 1960s before the “Pap” smear would become widely accepted as an effective method of screening and cancer prevention.
1928 – Genetic mutation is proposed as the origin of cancer. As an alternative to the infection theory of cancer, popular at the time because of the expansion of microbiology as a field of study, came the proposal that somatic mutation was the cause of cancer. As Mendel’s works were rediscovered in 1928, the field of genetics grew. The term “somatic mutation” had been coined in 1916.
1927 – Cancer is named one of the top three causes of death in America by U.S. Census Bureau.
1924 – Metabolic studies show that tumors exhibit anaerobic respiration. Whereas normal tissues use oxygen to break down nutrients for growth as their primary mode of respiration, it was observed that within tumors, cells respire anaerobically, fermenting sugars without oxygen. It will take several decades before hypoxia is revisited as a marker for tumors.

1900-1910

1915 – The first experimental animal model of chemically induced cancer is developed. Repeated tarring of rabbit skin caused tumors. The discovery added to early evidence for the theory of chemical carcinogenesis.
1913 – A group of volunteers establishes the American Society for the Control of Cancer, precursor to the American Cancer Society.
1907 – Sunlight exposure is linked to skin cancer. The first epidemiologic study of sunlight and skin cancer was reported; earlier observations had linked chronic skin conditions common in sailors to exposure to the radiation effects of the sun. Later work in animal models confirmed that skin cancer could be induced by ultraviolet light and sunlight.

19th Century

1844 – Peyrone’s choloride was first created by Italian chemist Michele Peyrone. For a long time, it was known as Peyrone’s chloride until the important discovery of cisplatin as a cancer treatment by Barnett Rosenberg, a biophysical chemist at Michigan State University.
1858 – Virchow was the first to deduce the origin of cancer cells from other cells, omnis cellula e cellula, meaning all cells come from cells.
1855 – Michigan State University is founded and is considered one of the first institutions in the United States to teach scientific agriculture, though not the oldest. More…

CREDITS AND ACKNOWLEDGMENTS

These milestones are a compilation of documents from many in the research community that contributed to the AACR Landmarks in Cancer Research 1907-2017, Research@MSU, National Cancer Institute, and NCI Legislative Timeline.