Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow

Interferon-α2b (IFN-α2b) is a highly active cytokine that belongs to the interferon-α (IFN-α) family. IFN-α2b has beneficial antiviral, antitumour, antiparasitic and immunomodulatory activities. Direct and indirect antiproliferative effects of IFN-α2b have been found to occur via multiple pathways, mainly the JAK-STAT pathway, in certain cancers. This article reviews mechanistic studies and clinical trials on IFN-α2b. Potential regulators of the function of IFN-α2b were also reviewed, which could be utilized to relieve the poor response to IFN-α2b. IFN-α2b can function not only by enhancing the systematic immune response but also by directly killing tumour cells. Different parts of JAK-STAT pathway activated by IFN-α2b, such as interferon alpha and beta receptors (IFNARs), Janus kinases (JAKs) and IFN‐stimulated gene factor 3 (ISGF3), might serve as potential target for enhancing the pharmacological action of IFN-α2b. Despite some issues that remain to be solved, based on current evidence, IFN-α2b can inhibit disease progression and improve the survival of patients with certain types of malignant tumours. More efforts should be made to address potential adverse effects and complications.