Review of the Agnostic-Type Treatment Approach: Treating Cancer by Mutations, Not by Location

Recent years has seen the discovery and description of genetic alterations responsible for oncogenesis in a wide variety of cancers, together with the finding that some markers are actionable and can be targeted by medications. Such developments have enabled cancer treatments to evolve from empirical palliative chemotherapy, with low chances of response or curative intent in most types of cancers, to targeted therapy, with some studies showing promising results in terms of improved overall response rates, overall survival and quality of life, although, like all new groups of medications, with specific adverse effect profiles. This treatment evolution is a major development in cancer therapy. Tumors were originally classified as solid or liquid tumors based on their location in the human body (solid organs or blood), which evolved into the medical specialties of medical oncology and clinical hematology, respectively. Subsequently, tumors were classified by the organ they originate from, in the belief that the origin of the tumor would guide its biological behavior and would faciliate understanding of their mechanism of spread and, potentially, of the best treatment approach. Although this latter approach has achieved some success over the many years it has been applied, there have been major disappointments, particularly in lung cancers for which palliative chemotherapy has only been able to provide a median survival of around 1 year and a complete remission rate of < 5%. We are now understanding that this concept of cancer pathophysiology is more complex, but also potentially simple, and that one or several molecular aberrations are probably responsible for the origin of each cancer. Various molecular alterations have been described, although the relevance of each alteration is not yet fully understood. In this article, we highlight clinical trial designs, biologic issues, and regulatory issues leading to the development of medications for tissue-agnostic treatment.