From oncolytic peptides to oncolytic polymers: A new paradigm for oncotherapy

Three Rounds of Stability-Guided Optimization and Systematical Evaluation of Oncolytic Peptide LTX-315

“…LTX-315 was derived from bovine lactoferricin (LFcinB), exhibiting striking anticancer effects against various drug-sensitive as well as drug-resistant cancer cell lines. − Especially, LTX-315 has been demonstrated to exhibit positive anticancer responses in multi-indication Phase I/II oncology trials (Clinical Trials.gov Identifier: NCT01223209, NCT01986426, and NCT01058616, and NCT03725605) . For most oncolytic peptides, the net positive charge, as well as the relative distribution of cationic and hydrophobic residues, are two crucial key factors for the membranolytic effect. ,,, Especially, most natural and artificially designed linear oncolytic peptides have been demonstrated to be rich in lysine (K) and arginine (R) residues, both of which tend to be degraded by various proteases. ,, In addition, previous studies indicated that linear peptides often suffer from poor stability against various proteolytic enzymes …”

“…42 For most oncolytic peptides, the net positive charge, as well as the relative distribution of cationic and hydrophobic residues, are two crucial key factors for the membranolytic effect. 10,35,43,44 Especially, most natural and artificially designed linear oncolytic peptides have been demonstrated to be rich in lysine (K) and arginine (R) residues, both of which tend to be degraded by various proteases. 26,31,45 In addition, previous studies indicated that linear peptides often suffer from poor stability against various proteolytic enzymes.…”

“…Cancer has become a global health challenge and a major barrier to improving life expectancy worldwide. , Despite considerable progress in anticancer strategies and anticancer drugs, cancer, especially drug-resistant refractory malignancies, remains the major cause of global morbidity and mortality . Among various anticancer strategies, chemotherapy is still the primary option, especially for the advanced and metastatic stages of cancers. , Nevertheless, traditional chemotherapy agents often suffer from potential drug resistance, lack of cancer selectivity, and severe toxicity. − Therefore, developing novel classes of anticancer agents with new mechanisms is of great importance. − Over the last two decades, peptide-based agents have represented a promising approach for cancer prevention and treatments. ,− Strikingly, peptides have exhibited multiple anticancer activities, such as cancer immunotherapy through blocking immune checkpoints, − cytotoxic peptides through membrane disruption/permeation effects, , as well as peptide-drug conjugates (PDCs) through targeting the specific receptor of cancer cells. ,− …”

“…Recently, oncolytic peptides possessing synergistic oncolytic-immunotherapy effect have emerged as one of the main subsets of anticancer peptides and potential anticancer agents. ,, Oncolytic peptides are a class of surface-acting membrane-disrupting peptides, such as CAMP-derived peptide (LL-37), bovine lactotransferrin (LTF)-derived peptides, animal venoms and toxins-derived peptides, as well as the synthetic oncolytic peptides represented by “peptide 11″, , SVS-1 and (KAAKKAA) 3 . , Oncolytic peptides could disrupt the integrity of cancer cell membrane, penetrate cells, and destroy the intracellular membrane, the combined actions of which could induce the rapid death of cancer cells. , …”

ACP-DRL: an anticancer peptides recognition method based on deep representation learning

“…These peptides display an exceptional capacity to selectively target and eliminate cancer cells via folding-dependent membrane disruption ( Aronson et al, 2018 ). On the one hand, ACPs therapy has been extensively researched and applied in preclinical and various stages of clinical trials against tumors ( Pelliccia et al, 2019 ; Liu et al, 2024 ). On the other hand, the time-consuming and costly process of identifying ACPs through biological experiments, as well as the limited number of available ACPs, have hindered its development.…”