Basic Research: Vital for Making Progress Against Cancer Basic research, together with translational and clinical studies and population sciences, has played a pivotal role in reducing the burden of cancer in the United States. Discoveries stemming from decades of basic research have provided the foundational knowledge, which has led to a 33 percent reduction in the overall cancer mortality rate over the last three decades (see Sidebar 6, p. 28). One example of how basic research contributes to progress against cancer is the development of small molecule inhibitors of Kirsten rat sarcoma viral oncogene homologue (KRAS), a protein that is essential for the growth and survival of normal cells and is altered in many cancers. Several teams of basic researchers simultaneously identified the human KRAS gene in 1982 (65). Subsequent discoveries linked KRAS activity with growth and survival of normal cells and identified alterations in the gene that were associated with human cancer (65). More recent studies have established that the KRAS gene is frequently mutated (see Sidebar 7, p. 30) in several cancer types, including cancers of the pancreas, lungs, and colon and rectum (66). Up until 2021, KRAS was considered an undruggable protein, and patients with cancer harboring KRAS mutations had limited treatment options. Thanks to the research-driven technological innovations, advances in synthetic chemistry and structural biology, and a deeper understanding of the genetic alterations in lung cancer, researchers The Research Cycle Advancing the Frontiers of Cancer Science and Medicine The medical research cycle is a self-driven process with a primary goal to save and improve lives. Findings from any type of basic research can lead to new questions and generate new hypotheses relevant to the practice of medicine. The discovery phase of the medical research cycle uncovers new targets for developing better and more effective treatments. Potential therapeutics can be designed and first tested in preclinical models mimicking normal and disease conditions to identify any harmful effects and determine initial dosing. The safety and efficacy of potential therapeutics are then tested in clinical trials. If an agent is safe and effective, it is approved for use in the clinic by the U.S. Food and Drug Administration (FDA). Importantly, observations made during the routine use of a new therapeutic can further improve its use or inform the development of others like it. Even for therapeutics that are not approved by FDA, observations from preclinical and/or clinical testing can spur future research efforts. In addition to fueling the development of safer and more effective therapeutics, scientific knowledge gathered through basic, translational, and clinical research, as well as from population science, informs evidence-based guidelines for cancer screening, preventive interventions, and other public health policies and regulations. Adapted from (4). Therapeutic Development Clinical Research (Clinical Trials) Clinical Practice (Standard of Care) Hypothesis Discovery & Validation NEW OBSERVATION NEW OBSERVATION NEW OBSERVATION BENCH BEDSIDE PRACTICE FIGURE 4 Understanding the Path to Cancer Development AACR Cancer Progress Report 2023 27
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