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Recent advances and applications of peptide–agent conjugates for targeting tumor cells

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  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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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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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Acknowledgements

Authors wish to thank Molecular Medicine Department and also Pharmaceutical Sciences Research Center of Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 7133654361, Iran

    Vahab Alamdari-palangi, Yasaman Naeimzadeh, Amir Tajbakhsh, Vahid Razban & Jafar Fallahi

  2. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Khojaste Rahimi Jaberi

  3. Medical Biotechnology Research Center, Arak University of Medical Sciences, Arak, Iran

    Mahshid Shahverdi

  4. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Amir Tajbakhsh

  5. Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sahar Khajeh

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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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