Abstract
Cancer became recently the leading cause of death in industrialized countries. Even though standard treatments achieve significant effects in growth inhibition and tumor elimination, they cause severe side effects as most of the applied drugs exhibit only minor selectivity for the malignant tissue. Hence, specific addressing of tumor cells without affecting healthy tissue is currently a major desire in cancer therapy. Cell surface receptors, which bind peptides are frequently overexpressed on cancer cells and can therefore be considered as promising targets for selective tumor therapy. In this review, the benefits of peptides as tumor homing agents are presented and an overview of the most commonly addressed peptide receptors is given. A special focus was set on the bombesin receptor family and the neuropeptide Y receptor family. In the second part, the specific requirements of peptide-drug conjugates (PDC) and intelligent linker structures as an essential component of PDC are outlined. Furthermore, different drug cargos are presented including classical and recent toxic agents as well as radionuclides for diagnostic and therapeutic approaches. In the last part, boron neutron capture therapy as advanced targeted cancer therapy is introduced and past and recent developments are reviewed.
Highlights
Cancer became recently the leading cause of death in industrialized countries
These chemotherapeutic drugs affect healthy cells that exhibit high proliferation rates like intestinal epithelium cells. This peripheral toxicity is the reason for frequently occurring side effects, which can vary from hair loss, peptide-drug conjugates (PDC) in Cancer Therapy anemia, bruising and bleeding to neuropathy and many more (Strebhardt and Ullrich, 2008)
Even though radiation therapy is often used in combination with surgery and chemotherapeutic modalities to increase the anti-tumor effect, long term cancer survivors have a higher risk for developing second malignancies because the radiation does harm genetic material of healthy tissue (Dracham et al, 2018)
Summary
Cardiovascular diseases were the leading cause of death among middle-aged adults globally. For the last 60 years, chemotherapy remained the trademark of cancer treatment (Gilman, 1963; DeVita and Chu, 2008) In this approach, highly cytotoxic drugs are systemically administered, which seek into rapidly dividing cancer cells. The generation of mAbs is very expensive as well as time-consuming and non-selective payload conjugation can lead to reduced product homogeneity (Nejadmoghaddam et al, 2019) Most of these drawbacks can be eliminated by using smaller biomolecules like peptides. Peptides are generally considered safe, since they feature low immunogenicity and produce non-toxic metabolites (Ahrens et al, 2012) Their low molecular weight leads to an enhanced penetration into solid tissues resulting in better anti-tumor effects (Firer and Gellerman, 2012; Hock et al, 2015). The increased payload loading can enhance the therapeutic effects due to the increased drug concentrations at the tumor site (Dubowchik et al, 2002; Böhme et al, 2016)
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