Treatment options for effective treatment of cancer with minimum off-target effects and
maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has
remained in the shadows of controversy since the past few decades; burgeoning evidence has started to
shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant
cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark
achievements in molecular oncology have ushered in a new era, and researchers have focused on the
identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are
visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of
transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin
C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However,
published data is insufficient and needs to be investigated comprehensively to enable basic and clinical
researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases
of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic
cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual
gaps, which need detailed and cutting-edge research.