Enhancing Anticancer Treatment Efficacy With Lycopene: A Comprehensive Review of Clinical and Preclinical Evidence

Lycopene (LYP), the red pigment found in tomatoes, is a non-provitamin A carotenoid recognized for its biological significance and anticancer potential. Beyond its direct anticancer effects, LYP has been shown to enhance the efficacy of various anticancer agents when used in combination. Herein, we have conducted a literature survey using PubMed and ClinicalTrials.gov databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to systematically review LYP's efficacy in combination therapy. A search in PubMed using the keywords "lycopene and combination and cancer" yielded 206 studies, while "lycopene and cancer" retrieved 27 clinical trials from ClinicalTrial.gov. After applying the defined eligibility criteria, 45 relevant studies were included: 37 unique to PubMed, six unique to ClinicalTrials.gov, and two common to both databases. These studies collectively demonstrate that LYP, when used in combination with other therapeutic agents, can modulate several key oncogenic signaling pathways, including JAK2, MAPK, Akt/mTOR, IGF-1R, Akt/EZH2/AR, and PPARγ/LXRα/ABCA1. Additionally, LYP influences the activity of NF-κB, IFN-γ, and Nrf2, and also modulates cellular processes such as autophagy, apoptosis, and antioxidant defense mechanisms. These alterations have been observed when LYP is combined with various anticancer therapeutics, including radiation therapy, photodynamic therapy, standard chemotherapeutic agents such as cisplatin, 5-fluorouracil, taxanes, and sorafenib, as well as several phytochemicals and other potential anticancer agents, across various cancers. Nevertheless, robust clinical validation is required to confirm the therapeutic potential of these combinations and to establish LYP as an effective adjuvant in cancer treatment.