Introduction
Cancer is a multifactorial and complex disease, which presents different clinical outcomes depending on the affected tissue and the genetic background of the patient (Luo, Solimini, & Elledge, 2009). Tumor cells express a variety of molecular targets involved in cancer progression and exhibit a deregulation in normal growth, proliferation and survival, among other vital functions (Hanahan & Weinberg, 2011). Because of its complexity, the huge variety of molecular targets involved and the high variability in therapeutic response, cancer has become a health problem worldwide and one the sickness most difficult to treat in the 21st century.
Commonly, traditional chemotherapeutical drugs target tumor cells by disrupting necessary cell products, such as DNA, RNA, or proteins (Huang et al., 2014). However, chemotherapy is also insufficient and highly toxic, because it does not specifically target tumor cells, causing many side effects in patients (Amit & Hochberg, 2010). Additionally, multidrug resistance (MDR) is the main reason by which chemotherapy fails to cure patients (Huang et al., 2014). Under these limitations, therapeutical strategies based on peptides are receiving increased attention.
There are several advantages of peptides, such as the small size, easy synthesis and modification, tumor penetrating ability and a good biocompatibility (Wu et al., 2014). A growing number of studies indicate that peptides may be beneficial for drug discovery and development. Peptides offer minimal immunogenicity, excellent tissue penetrability, low-cost manufacturability, and relatively easy of modify to enhance in vivo stability and biological activity, properties which make them ideal candidates for cancer treatment (Yavari, Mahjub, Saidijam, Raigani, & Soleimani, 2018).
Peptides have also demonstrated to play a role in cancer therapy, including early diagnosis, prognostic predictors, and directly in the treatment of cancer patients. Unlike other therapies, peptides seem to be more effective due to their specificity. Recently, some peptide-based treatments against cancer, such as peptide vaccines, have attracted increased attention. Anticancer activity of different peptides is attributed to a variety of mechanisms that restrict tumor growth. (Borghouts, Kunz, & Groner, 2005).
CIGB-552 is a synthetic peptide “first-in-class” that increases the level of the intracellular protein COMMD1 (Copper Metabolism Mur 1 Domain containing protein1) and inhibits the anti-apoptotic genes regulated by Nuclear Factor κB (NF-κB). CIGB-552 leads to the selective degradation of RelA, an NF-κB subunit, and induces apoptosis in multiple types of tumor cells in the absence of toxicity to normal cells. In addition, CIGB-552 inhibits the transcriptional activity of NF-κB induced by TNF-α and IL-1β in human colon cancer cells. The mechanism of action of CIGB-552 assumes a new-targeted anticancer therapy to regulate oncogenic-inflammatory activity of NF-κB in cancer cells, providing selectivity and specificity. This novel peptide has a potential application against solid tumors and inflammation-associated cancer including colorectal, breast and lung cancer, lymphomas and others.