Current research status of anti-cancer peptides: Mechanism of action, production, and clinical applications

Chinnadurai, Raj Kumar; Khan, Nazam; Meghwanshi, Gautam Kumar; Ponne, Saravanaraman; Althobiti, Maryam; Kumar, Rajender

doi:10.1016/j.biopha.2023.114996

Cited by 28 publications

(5 citation statements)

References 137 publications

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“…Противоопухолевые пептиды активно изучаются с конца прошлого века [11]. Показано, что большинство из них обладают относительно высокой неспецифической токсичностью.…”

Section: Discussionunclassified

Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Bozhenko,

Goncharov,

Kudinova

et al. 2024

Almanac of Clinical Medicine

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Background: Ras oncogene mutations leading to hyperactivation of the MAPK/ERK signaling pathway occur in 25% of all human tumors, and for gastrointestinal tumors, the frequency of Ras mutations amounts to 60%. The introduction of a Ras-GTPase inhibitor into clinical practice would increase the effectiveness of the treatment of socially significant diseases such as stomach and intestinal cancer. Aim: To select the optimal dose with a subsequent assessment of the safety of iRAS when administered to patients with gastrointestinal tract tumors, including those with peritoneal carcinomatosis. Materials and methods: This was a prospective open-label non-randomized phase I study for the assessment of safety and tolerability, with an adaptive design and determination of the maximally tolerated dose of the iRAS. Three dose levels were used (0.45 mg/kg, 0.9 mg/kg, 1.8 mg/kg) according to the "3 + 3" scheme. The study included 11 patients after surgery for stomach or colorectal cancer. The patients were administered PIPAC therapy with iRAS twice with a 7-days interval. The study duration was 28 ± 1 days. During the study, the patient monitoring included physical examination, assessment of vital signs, electrocardiography and echocardiography, laboratory parameters (hematology, clinical chemistry, coagulation tests, and urine analysis). Results: The anti-tumor iRAS agent demonstrated satisfactory tolerability of all doses studied, including the maximal 1.8 mg/kg dose. Vital sign and laboratory abnormalities were clinically non-significant and did not require additional therapeutic interventions. Statistically significant abnormalities were registered for total protein (p = 0.00028), white blood cell counts (p = 0.007), lymphocyte counts (p = 0.0008), and a number of other blood parameters; however, most of these abnormalities were within the physiological normal ranges. Vital signs such as electrocardiography and echocardiography parameters remained stable throughout the entire follow-up period (28 days after administration of the drug). There were short-term rises in body temperature, minor pains in the postoperative scar area. Conclusion: This trial of safety and tolerability of iRAS showed that no cases of dose-limiting toxicity in the studied dose range. The 1.8 mg/kg dose can be recommended for further clinical studies.

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Section: Discussionunclassified

Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Bozhenko,

Goncharov,

Kudinova

et al. 2024

Almanac of Clinical Medicine

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“…Among the anticancer compounds found in marine animals, in this review, a focus was put on peptides and their mechanisms of action in model systems in vitro. Cumulatively, anticancer peptides show several advantages compared to conventional chemotherapeutics, due to their low toxicity, biocompatibility, elevated specificity and selectivity and the low tendency to develop drug resistance [ 4 ]. Natural peptides have been modified in regard to their chemical structure, e.g., by methylation, acetylation or phosphorylation, as a strategy to improve their pharmacokinetic properties.…”

Section: Discussionmentioning

confidence: 99%

“…These peptides are heterogeneous and endowed with different secondary structures allowing them to be grouped into four categories as follows: α-helical, β-pleated sheets, random coil and cyclic [ 2 ]. Their anticancer activity is carried out through interference with intracellular homeostasis, such as plasmalemma integrity, cell cycle control, enzymatic activities and mitochondrial functions, ultimately acting as angiogenesis-, drug resistance- and metastasis-inhibiting agents, immune stimulators, differentiation inducers and necrosis or extrinsic/intrinsic apoptosis promoters [ 3 , 4 ].…”

Section: A Brief Insight Into Anticancer Peptidesmentioning

confidence: 99%

Natural Anticancer Peptides from Marine Animal Species: Evidence from In Vitro Cell Model Systems

Librizzi,

Martino,

Mauro

et al. 2023

Cancers

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Anticancer peptides are short and structurally heterogeneous aminoacidic chains, which display selective cytotoxicity mostly against tumor cells, but not healthy cells, based on their different cell surface properties. Their anti-tumoral activity is carried out through interference with intracellular homeostasis, such as plasmalemma integrity, cell cycle control, enzymatic activities and mitochondrial functions, ultimately acting as angiogenesis-, drug resistance- and metastasis-inhibiting agents, immune stimulators, differentiation inducers and necrosis or extrinsic/intrinsic apoptosis promoters. The marine environment features an ever-growing level of biodiversity, and seas and oceans are poorly exploited mines in terms of natural products of biomedical interest. Adaptation processes to extreme and competitive environmental conditions led marine species to produce unique metabolites as a chemical strategy to allow inter-individual signalization and ensure survival against predators, infectious agents or UV radiation. These natural metabolites have found broad use in various applications in healthcare management, due to their anticancer, anti-angiogenic, anti-inflammatory and regeneration abilities. The aim of this review is to pick selected studies that report on the isolation of marine animal-derived peptides and the identification of their anticancer activity in in vitro cultures of cancer cells, and list them with respect to the taxonomical hierarchy of the source organism.

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“…cGAS binds to its DNA ligand and forms a dimer, in which the DNA is sandwiched between two cGAS protomers. Active cGAS binds to ATP and GTP and catalyzes the condensation reaction of these two nucleotides to produce 2 ,3 -cyclic GMP-AMP (2 ,. Then, cGAMP binds to STING, and results in TANK-binding kinase 1-dependent phosphorylation of interferon regulatory factor 3 (IRF3).…”

Section: Cytokinesmentioning

confidence: 99%

“…Radiation therapy protects tissue that is not affected by the tumor, produces less damage and does not require hospitalization, but the application of radiotherapy depends on the type, size and location of tumors. Compared with these traditional therapies, tumor immunotherapy can kill tumor cells by activating the host's immune system [2,3]. The discipline of oncology has been undergoing an unprecedented revolution due to the massive advancement of immunotherapy in the treatment of cancer [4].…”

Section: Introductionmentioning

confidence: 99%

Innate Immunity in Cancer Biology and Therapy

Zhang

Xue

et al. 2023

IJMS

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Immunotherapies including adaptive immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have developed the treatment of cancer in clinic, and most of them focus on activating T cell immunity. Although these strategies have obtained unprecedented clinical responses, only limited subsets of cancer patients could receive long-term benefits, highlighting the demand for identifying novel targets for the new era of tumor immunotherapy. Innate immunity has been demonstrated to play a determinative role in the tumor microenvironment (TME) and influence the clinical outcomes of tumor patients. A thorough comprehension of the innate immune cells that infiltrate tumors would allow for the development of new therapeutics. In this review, we outline the role and mechanism of innate immunity in TME. Moreover, we discuss innate immunity-based cancer immunotherapy in basic and clinical studies. Finally, we summarize the challenges in sufficiently motivating innate immune responses and the corresponding strategies and measures to improve anti-tumor efficacy. This review could aid the comprehension of innate immunity and inspire the creation of brand-new immunotherapies for the treatment of cancer.

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Current research status of anti-cancer peptides: Mechanism of action, production, and clinical applications

Cited by 28 publications

References 137 publications

Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Natural Anticancer Peptides from Marine Animal Species: Evidence from In Vitro Cell Model Systems

Innate Immunity in Cancer Biology and Therapy

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