A novel hybrid peptide targeting EGFR-expressing cancers

Kohno, Masayuki; Horibe, Tomohisa; Haramoto, Mari; Yano, Yoshiaki; Ohara, Koji; Nakajima, Oumi; Matsuzaki, Katsumi; Kawakami, Koji

doi:10.1016/j.ejca.2010.10.021

Cited by 69 publications

(80 citation statements)

References 28 publications

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“…N. Papo and colleagues developed a novel lytic peptide composed of DL-amino acids, which selectively killed cancer cells in vitro and in vivo (13). However, because we found that this lytic sequence was not suitable to combine with targeting moiety, we modified the DL-amino acids sequence to appropriately induce modest cancer cells killing, with less toxicity to normal cells in a lower concentration (11). Similar to the lytic peptide previously reported, the new lytic sequence has positive charge and binds to negatively charged membranes (37) and subsequently lyses them (38).…”

Section: Discussionmentioning

confidence: 99%

“…To overcome these problems, a new hybrid peptide drug, which has a similar concept with immunotoxin but smaller molecular weight, has been developed (11). Anticancer hybrid peptide (type I) contains target-binding amino acids and toxic amino acid sequences.…”

Section: Introductionmentioning

confidence: 99%

“…In the toxic part of the hybrid peptide, we have used a new lytic peptide (11), which is stable when combined with targeting peptide with less toxic to normal cell lines when compared with original lytic peptide composed of a 15 amino acid diastereomer composed of D-and L-amino acids (13).…”

Section: Introductionmentioning

confidence: 99%

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Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

Yang

Horibe

Kohno

et al. 2012

Molecular Cancer Therapeutics

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Interleukin-4 receptor a (IL-4Ra) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Ra-lytic peptide that targets the IL-4Ra chain. The IL-4Ra-lytic peptide contains a target moiety to bind to IL-4Ra and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL-4Ra-lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Ra-lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Ra, determined by quantitative real-time PCR. The IC 50 ratios of the lytic peptide to the IL-4Ra-lytic peptide correlated well with the expression levels of IL-4Ra on cancer cells (r ¼ 0.80). In addition, IL-4Ra-lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Ra-lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Ra-positive solid cancers. Mol Cancer Ther; 11(1); 235-43. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

Yang

Horibe

Kohno

et al. 2012

Molecular Cancer Therapeutics

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“…Epidermal growth factor receptor (EGFR) is over expressed in OSCC tissues about 71%-88% [96]. Recently, a hybrid peptide as a new agent of EGFRtargeting therapy was designed and synthesized, which contains an EGFR-targeting peptide of YHWYGYTPQNVI and a lytic peptide of KLLLKLLKKLLKLLKKK-OH (bold letters are D-amino acids) [97]. The hybrid peptide could kill EGFR-expressing cells through the combined process of specific binding to EGFR on the cell surface and subsequently disintegrate cell membranes.…”

Section: Egfr Ligandmentioning

confidence: 99%

Design and Modification of Anticancer Peptides

Hu¹,

Chen²,

Zhao³

et al. 2016

Drug Des

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Cancer is a great concern in the public health and development of novel therapeutic agent or strategy become urgently. Anticancer peptides (ACPs) have become promising anticancer drug candidate molecules due to their several extraordinary properties, such as small size, high activity, low immunogenicity, good biocompatibility, diversity of sequence and more modification sites for the functional molecules. However, the low stability and short half-life of peptides are the major barriers for the application. In this review, we focus on the methods of peptide design and modification to improve the stability, half-life time and specificity of ACPs, which including amino acid substitution, cyclization, hybridization, fragmentization, modification of C-and N-terminal of peptide by polymer or targeting molecules, etc.modification of C-and N-terminal of peptide by polymer or targeting molecules, etc. The schematic diagram of major design and modification strategies of ACPs are shown in Figure 1.

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“…There are strategies to overcome these limitations and their consequences (Wu et al 2014), including amino acid substitution (Kohno et al 2011), fusion of peptides (Yang et al 2008), and peptide conjugation with chemotherapeutic drugs (Zhao et al 2012). …”

Section: Peptide-based Strategies For Cancermentioning

confidence: 99%

Anticancer Peptides: Prospective Innovation in Cancer Therapy

Gaspar

Castanho

2016

Host Defense Peptides and Their Potential as Therapeutic Agents

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Current cancer treatments require improvements in selectivity and efficacy. Surgery, radiation, and chemotherapy approaches result in patient's suffering over time due to the development of severe side-effects that simultaneously condition adherence to therapy. Biologically active peptides, in particular antimicrobial peptides (AMPs), are versatile molecules in terms of biological activities. The cytotoxic activities of several AMPs turn this group of molecules into an amazing pool of new templates for anticancer drug development. However, several unmet challenges limit application of peptides in cancer therapy. The mechanism(s) of action of the peptides need better description and understanding, and innovative targets have to be discovered and explored, facilitating drug design and development. In this chapter, we explore the natural occurring AMPs as potential new anticancer peptides (ACPs) for cancer prevention and treatment. Their modes of action, selectivity to tumor compared to normal cells, preferential targets, and applications, but also their weaknesses, are described and discussed.

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A novel hybrid peptide targeting EGFR-expressing cancers

Cited by 69 publications

References 28 publications

Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

Design and Modification of Anticancer Peptides

Anticancer Peptides: Prospective Innovation in Cancer Therapy

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