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Review
. 2024 Mar 2;16(5):1032.
doi: 10.3390/cancers16051032.

Peptide Therapeutics: Unveiling the Potential against Cancer-A Journey through 1989

Othman Al Musaimi  1   2
Affiliations
Review

Peptide Therapeutics: Unveiling the Potential against Cancer-A Journey through 1989

Othman Al Musaimi. Cancers (Basel). .

Abstract

The United States Food and Drug Administration (FDA) has approved a plethora of peptide-based drugs as effective drugs in cancer therapy. Peptides possess high specificity, permeability, target engagement, and a tolerable safety profile. They exhibit selective binding with cell surface receptors and proteins, functioning as agonists or antagonists. They also serve as imaging agents for diagnostic applications or can serve a dual-purpose as both diagnostic and therapeutic (theragnostic) agents. Therefore, they have been exploited in various forms, including linkers, peptide conjugates, and payloads. In this review, the FDA-approved prostate-specific membrane antigen (PSMA) peptide antagonists, peptide receptor radionuclide therapy (PRRT), somatostatin analogs, antibody-drug conjugates (ADCs), gonadotropin-releasing hormone (GnRH) analogs, and other peptide-based anticancer drugs are analyzed in terms of their chemical structures and properties, therapeutic targets and mechanisms of action, development journey, administration routes, and side effects.

Keywords: ADC; PDC; antineoplastic; cancer; chemotherapy; drugs; imaging; oncology; peptides; theragnostic; tumor.

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Conflict of interest statement

The author declares no conflicts of interest.

Figures

Figure 1
Figure 1
FDA-approved peptides from 1922 to 2023. Each bar represents a period of 10 years; however, due to the limited number of approvals, for the period between 1922 and 1980, one bar was assigned.
Figure 2
Figure 2
Development timelines of peptide-based anticancer drugs.
Figure 3
Figure 3
FDA-approved anticancer peptides (1989–2023). ADC, antibody drug conjugate; GnRH, gonadotropin-releasing hormone; PRRT, peptide receptor radionuclide therapy; PSMA, prostate-specific membrane antigen.
Figure 4
Figure 4
Chemical structure of 68Ga-PSMA-11. Blue, PSMA inhibitor; green, linker; red, chelator; black, radionuclide.
Figure 5
Figure 5
Chemical structure of piflufolastat F 18. Blue, PSMA inhibitor; green, pyridine-3-carbonyl; black, radionuclide.
Figure 6
Figure 6
Chemical structure of Pluvicto. Blue, PSMA inhibitor; red, chelator; black, radionuclide.
Figure 7
Figure 7
Chemical structure of flotufolastat F 18. Blue, PSMA inhibitor; red, chelator; black, radionuclide.
Figure 8
Figure 8
Chemical structure of depreotide. Pink, radionuclide.
Figure 9
Figure 9
Chemical structure of 68Ga-DOTATATE. Blue, octreotate; red, chelator; black, radionuclide.
Figure 10
Figure 10
Chemical structure of [177Lutetium]Lu-DOTA-TATE. Blue, octreotate; red, chelator; black, radionuclide.
Figure 11
Figure 11
Chemical structure of 68Ga-DOTATOC. Blue, octreotide; red, chelator; black, radionuclide.
Figure 12
Figure 12
Chemical structure of 64Cu-DOTATATE. Blue, octreotate; red, chelator; black, radionuclide.
Figure 13
Figure 13
Chemical structure of octreotide. Blue: disulfide bridge.
Figure 14
Figure 14
Chemical structure of Lanreotide. Blue: disulfide bridge.
Figure 15
Figure 15
Payload release mechanism in ADCs. Cathepsin B for Val-Cit, cathepsin B and cathepsin L for GGFG linker. Green, maleimide (caproyl) hexanoyl; black, linker; red, spacer; pink, payload; Orange, cathepsin B or cathepsin L.
Figure 16
Figure 16
The chemical structure of the natural dolastatin 10, MMAE, and MMAF. Blue: differences from the natural dolastatin 10.
Figure 17
Figure 17
Chemical structure of enfortumab vedotin-ejfv. Green, maleimide (caproyl) hexanoyl; black, linker; red, spacer; pink, payload.
Figure 18
Figure 18
Chemical structure of polatuzumab vedotin-piiq. Green, maleimide (caproyl) hexanoyl; black, linker; red, spacer; pink, payload.
Figure 19
Figure 19
Chemical structure of fam-trastuzumab deruxtecan-nxki. Green, maleimide (caproyl) hexanoyl; black, linker; blue, spacer; pink, payload.
Figure 20
Figure 20
Chemical structure of belantamab mafodotin-blmf. Green, maleimide (caproyl) hexanoyl; pink, payload.
Figure 21
Figure 21
Chemical structure of tisotumab vedotin-tftv. Green, maleimide (caproyl) hexanoyl; black, linker; red, spacer; pink, payload.
Figure 22
Figure 22
Chemical structure of loncastuximab tesirine-lpyl. Green, maleimide ethanoyl linked to polyethylene glycol; black, linker; red, spacer; pink, payload.
Figure 23
Figure 23
Gonadotropin-releasing hormone (GnRH) mechanism of action. LH, luteinizing hormone; FSH, follicle-stimulating hormone. Adapted from [124].
Figure 24
Figure 24
Chemical structure of goserelin.
Figure 25
Figure 25
Chemical structure of leuprolide.
Figure 26
Figure 26
Chemical structure of nafarelin.
Figure 27
Figure 27
Chemical structure of triptorelin.
Figure 28
Figure 28
Chemical structure of histrelin.
Figure 29
Figure 29
Chemical structure of ganirelix.
Figure 30
Figure 30
Chemical structure of cetrorelix.
Figure 31
Figure 31
Chemical structure of abarelix.
Figure 32
Figure 32
Chemical structure of degarelix.
Figure 33
Figure 33
Chemical structure of bortezomib.
Figure 34
Figure 34
Chemical structure of carfilzomib.
Figure 35
Figure 35
Chemical structure of melphalan flufenamide.
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