1. Using Pharmacology to Squeeze the Life Out of Childhood Leukemia, and Potential Strategies to Achieve Breakthroughs in Medulloblastoma Treatment
- Author
-
Juwina Wijaya, John D. Schuetz, and Tomoka Gose
- Subjects
0301 basic medicine ,Childhood leukemia ,Combination therapy ,Pharmacology ,Brain cancer ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Animals ,Humans ,Medicine ,Review Articles ,Childhood Acute Lymphoblastic Leukemia ,Randomized Controlled Trials as Topic ,Drug scheduling ,Medulloblastoma ,Brain Neoplasms ,business.industry ,Disease classification ,Cancer ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,030104 developmental biology ,Molecular Medicine ,business ,030217 neurology & neurosurgery - Abstract
Eliminating cancer was once thought of as a war. This analogy is still apt today; however, we now realize that cancer is a much more formidable enemy than scientists originally perceived, and in some cases, it harbors a profound ability to thwart our best efforts to defeat it. However, before we were aware of the complexity of cancer, chemotherapy against childhood acute lymphoblastic leukemia (ALL) was successful because it applied the principles of pharmacology. Herein, we provide a historic perspective of the experience at St. Jude Children's Research Hospital. In 1962, when the hospital opened, fewer than 3% of patients experienced durable cure. Through judicious application of pharmacologic principles (e.g., combination therapy with agents using different mechanisms of action) plus appropriate drug scheduling, dosing, and pharmacodynamics, the survival of patients with ALL now exceeds 90%. We contrast this approach to treating ALL with the contemporary approach to treating medulloblastoma, in which genetics and molecular signatures are being used to guide the development of more-efficacious treatment strategies with minimal toxicity. Finally, we highlight the emerging technologies that can sustain and propel the collaborative efforts to squeeze the life out of these cancers. SIGNIFICANCE STATEMENT: Up until the early 1960s, chemotherapy for childhood acute lymphoblastic leukemia was mostly ineffective. This changed with the knowledge and implementation of rational approaches to combination therapy. Although the therapeutics of brain cancers such as medulloblastoma are not as refined (in part because of the blood-brain barrier obstacle), recent extraordinary advances in knowledge of medulloblastoma pathobiology has led to innovations in disease classification accompanied with strategies to improve therapeutic outcomes. Undoubtedly, additional novel approaches, such as immunological therapeutics, will open new avenues to further the goal of taming cancer.
- Published
- 2020