Enhancing the anticancer effects of 5-fluorouracil: current challenges and future perspectives

Biomed J. Mar-Apr 2015;38(2):111-6. doi: 10.4103/2319-4170.130923.

Abstract

5-Flurouracil (5-FU), a pyrimidine analog, was originally designed to prevent tumor cell growth. However, since the identification of its tumor inhibitory activity in 1957, substantial evidence has demonstrated that 5-FU could also harness the host immune system to prevent cancer progression. 5-FU sensitizes tumor cells to Natural Killer (NK) and CD8 T cell-driven cytotoxicity. We have also recently shown that 5-FU could selectively eliminate Myeloid Derived Suppressor Cells (MDSCs), which accumulate during cancer progression and compromise anticancer immune responses. The ability of 5-FU to trigger direct tumor cell death, enhance immune effector cell activation and eliminate immunosuppressive MDSCs explains its capacity to relieve tumor-induced immunosuppression and restore anticancer immune responses. Combination therapies using 5-FU with other chemotherapeutic agents, immunomodulators, or vaccines have further enhanced the clinical benefit of 5-FU. Here, we discuss how the increased understanding of the immune-driven effects of 5-FU prompts the design of relevant cancer chemoimmunotherapy strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects*
  • Fluorouracil / pharmacology*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Fluorouracil