Tumor-Agnostic Therapy—The Final Step Forward in the Cure for Human Neoplasms?

Abstract

Cancer accounted for 10 million deaths in 2020, nearly one in every six deaths annually. Despite advancements, the contemporary clinical management of human neoplasms faces a number of challenges. Surgical removal of tumor tissues is often not possible technically, while radiation and chemotherapy pose the risk of damaging healthy cells, tissues, and organs, presenting complex clinical challenges. These require a paradigm shift in developing new therapeutic modalities moving towards a more personalized and targeted approach. The tumor-agnostic philosophy, one of these new modalities, focuses on characteristic molecular signatures of transformed cells independently of their traditional histopathological classification. These include commonly occurring DNA aberrations in cancer cells, shared metabolic features of their homeostasis or immune evasion measures of the tumor tissues. The first dedicated, FDA-approved tumor-agnostic agent’s profound progression-free survival of 78% in mismatch repair-deficient colorectal cancer paved the way for the accelerated FDA approvals of novel tumor-agnostic therapeutic compounds. Here, we review the historical background, current status, and future perspectives of this new era of clinical oncology.

Keywords

• tumor-agnostic philosophy
• pan-cancer mutations
• biomarkers
• next-generation sequencing