Commentary on Alfred G. Knudson, Jr.: 'Hereditary Cancer, Oncogenes, and Antioncogenes'

摘要

The original studies, reviews, and essays of Alfred G. Knudson, Jr. have shaped a conversation around the process of oncogenesis, and more specifically tumor suppression, for more than five decades. As a body of work, Knudson's studies and writings embody the full spirit of Einstein's quote above, exemplifying the time-honored scientific concept that careful work, solid data, attention to the work of the field as well as one's own, and a large dose of insight and imagination synergize to produce major conceptual advances (wholeheartedly acknowledging that imagination alone is not key to progress, but imagination rooted in the fertile soil of experimentation and collaboration can be transformational). Knudson, of course, is best known for the "two-hit hypothesis" that predicted loss of two alleles of a tumor-suppres-sive gene, or antioncogene, as they were first known, would be sufficient to instigate hereditary pediatric tumors, with retino-blastoma the signature example (1). With time and tireless study by myriad researchers, the fundamental truth of this concept has come to light, particularly for retinoblastoma. Nevertheless, the route to our current understanding of cancer genetics has been arduous and has revealed both important nuances and new, overarching concepts that have provided both conundrums and opportunities for therapy well beyond the wildest dreams of decades past.