Abstract
Background
Cancer, being a complex disease, presents a major challenge for the scientific and medical communities. Peptide therapeutics have played a significant role in different medical practices, including cancer treatment.
Method
This review provides an overview of the current situation and potential development prospects of anticancer peptides (ACPs), with a particular focus on peptide vaccines and peptide-drug conjugates for cancer treatment.
Results
ACPs can be used directly as cytotoxic agents (molecularly targeted peptides) or can act as carriers (guiding missile) of chemotherapeutic agents and radionuclides by specifically targeting cancer cells. More than 60 natural and synthetic cationic peptides are approved in the USA and other major markets for the treatment of cancer and other diseases. Compared to traditional cancer treatments, peptides exhibit anticancer activity with high specificity and the ability to rapidly kill target cancer cells. ACP's target and kill cancer cells via different mechanisms, including membrane disruption, pore formation, induction of apoptosis, necrosis, autophagy, and regulation of the immune system. Modified peptides have been developed as carriers for drugs, vaccines, and peptide–drug conjugates, which have been evaluated in various phases of clinical trials for the treatment of different types of solid and leukemia cancer.
Conclusions
This review highlights the potential of ACPs as a promising therapeutic option for cancer treatment, particularly through the use of peptide vaccines and peptide–drug conjugates. Despite the limitations of peptides, such as poor metabolic stability and low bioavailability, modified peptides show promise in addressing these challenges.
Graphical abstract
Various mechanism of action of anticancer peptides. Modes of action against cancer cells including: inducing apoptosis by cytochrome c release, direct cell membrane lysis (necrosis), inhibiting angiogenesis, inducing autophagy-mediated cell death and immune cell regulation.
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Data accessibility
This article does not contain any additional data.
Abbreviations
- ACPs:
-
Anticancer peptides
- PDCs:
-
Peptide–drug conjugates
- HNP-1:
-
Human neutrophil peptide
- LfcinB:
-
Lactoferrin
- GHRH:
-
Growth hormone-releasing hormone
- STAT3:
-
Signal transducer and activator of transcription 3
- GSH:
-
Glutathione
- ADCs:
-
Antibody–drug conjugates
- mAb:
-
Monoclonal antibody
- USFDA:
-
US Food and Drug Administration
- BBB:
-
Blood–brain barrier
- SORT1:
-
Sortilin 1
- DTX:
-
Docetaxel
- NSCLC:
-
Non-small cell lung cancer
- HDM-2:
-
Human double minute 2
- Apaf-1:
-
Apoptotic protease-activating factor-1
- ROS:
-
Reactive oxygen species
- TP53:
-
Tumor protein 53
- AIF:
-
Apoptosis-inducing factor
- EndoG:
-
Endonuclease G
- PLP2:
-
Proteolipid protein 2
- DAMPs:
-
Damage-associated molecular patterns
- HMGB1:
-
High-mobility group protein B1
- VEGF:
-
Vascular endothelial growth factor
- PDGF:
-
Platelet-derived growth factor
- FGF:
-
Fibroblast growth factor
- CK2:
-
Casein kinase 2
- MMP:
-
Matrix metalloproteinase
- VEGF-A:
-
Vascular endothelial growth factor
- ALA-A2:
-
Alpha-lactalbumin-A2
- IC50:
-
Half maximal inhibitory concentration
- DCs:
-
Dendritic cells
- Treg:
-
Regulatory T cell
- IFN-γ:
-
Interferon-gamma
- HLA:
-
Human leukocyte antigen
- IL-2:
-
Interleukin-2
- PEG:
-
Polyethylene glycol
- MOMP:
-
Mitochondrial outer membrane permeabilization
- Cyt c:
-
Cytochrome c
- AIF:
-
Apoptotic-inducing factor
- mPTP:
-
Mitochondrial permeability transition pore
- IMM:
-
Inner mitochondria membrane
- VDAC:
-
Voltage-dependent anion channels
- MTD:
-
Mitochondrial-targeting domain
- UCPVax:
-
Universal cancer peptide-based vaccine
- RhoC:
-
Ras homolog gene family member C
- SSRT2:
-
Somatostatin receptor-2
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Authors wish to thank Molecular Medicine Department and also Pharmaceutical Sciences Research Center of Shiraz University of Medical Sciences.
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VAP presented the idea. YN prepared the figures. The article was jointly written by VAP, KHRJ, MSh, YN, and AT under the supervision of AT, VR, and JF. AT drafted the manuscript. All authors have read and agreed to the published version of the manuscript.
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Alamdari-palangi, V., Jaberi, K.R., Shahverdi, M. et al. Recent advances and applications of peptide–agent conjugates for targeting tumor cells. J Cancer Res Clin Oncol 149, 15249–15273 (2023). https://doi.org/10.1007/s00432-023-05144-9
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DOI: https://doi.org/10.1007/s00432-023-05144-9