Current therapeutic approaches and promising perspectives of using bioengineered peptides in fighting chemoresistance in triple-negative breast cancer

Azari, Mandana; Bahreini, Farbod; Uversky, Vladimir N.; Rezaei, Nima

doi:10.1016/j.bcp.2023.115459

“…Treatment of triple-negative breast cancer is challenging due to limited treatment options, as molecular-targeted therapies are ineffective, and its significant metastatic potential and poor prognosis. − In the clinical setting, cytotoxic agents such as cisplatin and paclitaxel are mainly used for the treatment. To develop molecular-targeted agents for treating this intractable cancer, we focused on the chemokine receptor CXCR4 as a potential target because CXCR4 is involved in metastasis and is highly expressed in breast cancer cells, especially metastatic cancer cells .…”

Section: Discussionmentioning

confidence: 99%

“…14,18 The proapoptotic domain, KLAK, fused with the targeting ligands such as tumor-homing peptide, antibody, and natural ligand has gained much attention as one of the molecular-targeted therapies for cancer and is being developed for clinical translation. 3 In this study, we exploited a CXCR4 antagonist CTCE-9908 and constructed the CXCR4-targeted KLAK conjugate (CTCE-KLAK). We investigated the in vitro cytotoxic activity and mode of cell death of the CTCE-KLAK conjugate in breast cancer cell lines.…”

Section: ■ Introductionmentioning

confidence: 99%

“…It shows a higher recurrence rate, more significant metastatic potential, and a lower overall survival rate than other breast cancers. For treating this subtype of cancer, molecular-targeted therapies are largely ineffective, and chemotherapy using cytotoxic agents is currently the primary systemic treatment option . To effectively treat triple-negative breast cancer, new therapeutic targets need to be explored.…”

Section: Introductionmentioning

confidence: 99%

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CXCR4-Targeted Necrosis-Inducing Peptidomimetic for Treating Breast Cancer

Akonnor

¹

,

Makise

²

,

Kuniyasu

³

2023

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Triple-negative breast cancer is an aggressive subtype with a high recurrence rate, potential for metastasis, and a poor prognosis. The chemokine receptor, CXCR4, is a promising molecular target in breast cancer therapy. Here, we have developed a CXCR4-targeted antitumor peptidomimetic (named CTCE-KLAK), which is a fusion of the CXCR4 receptor antagonist CTCE-9908 and the D-form of proapoptotic peptide (KLAKLAK)2, for the treatment of breast cancer. First, we investigated the in vitro antitumor activity of CTCE-KLAK against various breast cancer cells and noncancerous mammary epithelial cells. CTCE-KLAK showed cell-selective cytotoxicity and induced rapid necrotic cell death in breast cancer cells but not in normal cells. In contrast, unconjugated peptides such as the carboxylate analogues of CTCE-9908 and D(KLAKLAK)2 were not cytotoxic to these cells. The tumor selectivity of CTCE-KLAK for cytotoxic activity depends on its internalization into tumor cells. There was no cleavage of caspase-3, caspase-7, or PARP1 in CTCE-KLAK-treated cells. In addition, cell death by CTCE-KLAK was not prevented by z-VAD-fmk, a pan-caspase inhibitor that inhibits cisplatin-induced cell death. These data indicate that the CTCE-KLAK conjugate is a cell-selective inducer of necrosis. Furthermore, we evaluated the in vivo antitumor activity of CTCE-KLAK in the 4T1 mouse metastatic breast cancer model. Intravenous administration of CTCE-KLAK significantly inhibited tumor growth and lung metastasis. Together, these findings suggest that the necrosis-inducing peptidomimetic CTCE-KLAK is a promising CXCR4-targeted agent for treating triple-negative breast cancer.

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“…Chemoresistance in OS immunotherapy [28] is the main problem in MBD in general and PBD in particular [29]. This problem increases after long-term treatments due to its acquired and accumulated nature [30][31]. It becomes more complicated after including tumorigenesis, metastasis, and immune evasion, as stated in our previous paper [32].…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi¹,

Miskon²

2023

Preprint

0

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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“…Chemoresistance in OS immunotherapy [ 28 ] is the main problem in MBD in general and PBD in particular [ 29 ]. This problem increases after long-term treatments due to its acquired and accumulated nature [ 30 , 31 ]. Chemoresistance develops over time, limiting clinical application and raising concerns about efficacy and systemic toxicity [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi

¹

,

Miskon

²

2023

Molecules

17

0

View full text Add to dashboard Cite

Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

show abstract

Current therapeutic approaches and promising perspectives of using bioengineered peptides in fighting chemoresistance in triple-negative breast cancer

Cited by 10 publications

References 166 publications

CXCR4-Targeted Necrosis-Inducing Peptidomimetic for Treating Breast Cancer

CXCR4-Targeted Necrosis-Inducing Peptidomimetic for Treating Breast Cancer

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

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