OncoDrugs 2014, 2(1):1e-2e Biological & Adjuvant Therapies

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Biological and adjuvant therapies, new trends in oral cancer treatment

Editorial

AUTHORS: Marcello Iriti1*

and Elena Maria Varoni2

AFFILIATIONS: 1Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy. 2Department of Biomedi-cal, Surgical and Dental Sciences, Milan State University, Milan, Italy

* CORRESPONDING AUTHOR: via G. Celoria 2, 20133 Milan, Italy; marcello.iriti@unimi.it

NEW TARGETED therapy for the treatment of oral squamous cell carcinoma (OSCC) consists of monoclonal anti-bodies (mAbs) against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR), fre-quently overexpressed in these cancer. In addition, tyrosine

kinase inhibitors (TKI) have been developed to target both re-ceptors. While mAbs are large proteins that have to be adminis-tered parenterally to avoid degradation in the gastrointestinal tract, TKI are small molecules able to be absorbed after oral administration.

Figure 1. Multi-therapies in oral cancer treatment.

Anti-EGFR O

O O H

O H

O H

O H

O

O H

O H

O H O H

Epigallocatechin-3-gallate

Camellia sinensis (tea)

Cl

Cl

Pt

NH3

NH3

Cisplatin

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Cetuximab and Bevacizumab are the most widely anti-EGFR and anti-VEGFR mAbs, respectively, and both humanised chi-meric mAbs have been approved by US Food and Drug Ad-ministration (FDA) and European Medicines Agency (EMA) (Fig 1). Among TKI, Gefitinib and Sorafenib, approved by FDA and EMA, inhibit EGFR and VEGFR tyrosine kinase activities, respectively (Dorsey and Agulnik, 2013). In the last decade, combination of conventional anticancer therapies with bioactive phytochemicals has gained considerable relevance. Addi-tive/synergistic effects have been attributed to this new strategy of cancer treatment, as well as decreased toxicity to non-target cells and amelioration of adverse side effects due to reduced doses of the administered anticancer drug (Lecumberri et al. 2013). Among phytochemicals used as chemosensitizers in ad-juvant therapy, epigallocatechin-3-gallate (EGCG, a flavonoid from green tea) and curcumin (diferuoylmethane, a polyphenol from Curcuma longa) have been particularly studied at preclini-cal level (Fig. 1). Many molecular mechanisms of EGCG- and curcumin-mediated chemosensitization have been advocated, including decreased expression and activity of multidrug resis-tance (MDR) proteins (Iriti and Varoni, 2013; Vinod et al. 2013). Increasing failure in cancer chemotherapy is mainly at-tributed to drug resistance of cancer cells. Mechanisms respon-sible for chemoresistance include defective apoptotic machin-ery, altered molecular targets, decreased drug uptake and MDR, i.e. overexpression of drug efflux pumps. Activation of MDR pathway is the most frequent phenomenon by which cancer cells elude chemotherapy (Patel et al. 2013, Rose-James et al. 2013). The efficacy of EGCG and curcumin as adjuvants in cancer

therapy has been investigated in many in vitro/in vivo studies, in combination with chemotherapeutic agents as doxorubicin, cis-platin, paclitaxel and 5-fluorouracil (reviewed in Lecumberri et al. 2013 and Vinod et al. 2013). Interestingly, EGCG protected both acinar and ductal salivary gland cells from -radiation- or cisplatin-induced injury (Yamamoto et al. 2004), and, in clinical trials on oral premalignant conditions, both curcumin and EGCG reduced lesion size in leukoplakia and submucous fibro-sis (Kim et al. 2010; Rai et al. 2010). However, sporadic an-tagonistic interactions between phytochemicals and drugs have also been documented (Ge et al. 2011). To conclude, even if surgery still represents the current gold standard of care to remove the whole clinically visible cancer mass achieving tu-mour-free margins, in addition to the removal of affected or suspect locoregional lymph-nodes (van der Waal, 2013), as well as radiotherapy is usually applied in combination to surgery or in those cases of unresectable disease (Bredell et al., 2012), multi-therapies may represent effective and promising strategies in modern anticancer research.

Conflict of Interests

The authors declare no conflict of interests.

Received: 06/03/2014

Accepted: 08/03/2014

Published: 11/03/2014

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