New insights into the anticancer therapeutic potential of maytansine and its derivatives

Zafar, Sameen; Armaghan, Muhammad; Khan, Khushbukhat; Hassan, Nabil; Sharifi‐Rad, Javad; Habtemariam, Solomon; Kieliszek, Marek; Butnariu, Monica; Bagiu, Iulia Cristina; Bagiu, Radu Vasile; Cho, William C.

doi:10.1016/j.biopha.2023.115039

Cited by 13 publications

(7 citation statements)

References 174 publications

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“…DM1 is a microtubule-interfering agent with potent and broad-spectrum antitumor activity but cannot be used alone due to its strong systemic toxicity. − Nanomedicines are believed to improve the pharmacokinetics and reduce the side effects of chemotherapeutics, , which may expand the clinical application of DM1. In particular, targeted delivery nanosystems that can stably load DM1 to prevent leakage and deliver it specifically to the tumor site are desired, but limited research is currently available.…”

Section: Resultsmentioning

confidence: 99%

CD7 Nanobody-Based Immuno-Nanotoxin for Targeted Treatment of T-Cell Acute Lymphoblastic Leukemia

Dong,

You,

Zhang

et al. 2024

ACS Appl. Nano Mater.

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T-cell acute lymphoblastic leukemia (T-ALL) has been plagued by high relapse and mortality rates due to the lack of available targeted treatment options in the clinic. Herein, a CD7specific immuno-nanotoxin based on anti-CD7 nanobody-modified polymersome-mertansine nanoconjugates (aCD7-Ps-DM1) was engineered to enable effective and targeted chemotherapy of orthotopic T-ALL in vivo. aCD7-Ps-DM1 with regulable aCD7 density showed no DM1 leakage while rapid DM1 release under reducing conditions. The aCD7-Ps-DM1 immuno-nanotoxin efficiently targeted CD7-positive CCRF-CEM T-ALL cells, leading to 5-fold and >13-fold greater anti-ALL activity than that of nontargeted Ps-DM1 and CD7-negative B-ALL cell lines, respectively. In orthotopic CCRF-CEM T-ALL-bearing mice, repetitive (multiple) dosing of aCD7-Ps-DM1 persistently inhibited leukemia progression and infiltration in the bone marrow, blood, and organs, leading to significantly improved survival. This CD7-specific immuno-nanotoxin may offer a potential targeted treatment strategy for T-ALL.

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Section: Resultsmentioning

confidence: 99%

CD7 Nanobody-Based Immuno-Nanotoxin for Targeted Treatment of T-Cell Acute Lymphoblastic Leukemia

Dong,

You,

Zhang

et al. 2024

ACS Appl. Nano Mater.

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“…However, “non-topoisomerase I” ADCs have been studied and are currently under preclinical and clinical investigation in sarcomas [ 100 , 114 ], and potentially some of these mAb targets could also be explored with a topoisomerase I-based ADC. Several non-topoisomerase I payloads have been considered for the treatment of sarcomas and include tubulin-targeting drugs (such as MMAE or MMAF), or DNA-targeting drugs (with DNA alkylating agents such as duocarmycins, pyrrolobenzodiazepines, calicheamicins, or anthracycline), or microtubule destabilizing agents (such as maytansine) [ 100 , 115 , 116 ]. The advantages of these ADCs include the selective targeting of the sarcoma tumor and the potential for an improved therapeutic index, while one of the disadvantages may be the potential for resistance to develop, as with conventional chemotherapy [ 117 , 118 ].…”

Section: Discussionmentioning

confidence: 99%

Current Role of Topoisomerase I Inhibitors for the Treatment of Mesenchymal Malignancies and Their Potential Future Use as Payload of Sarcoma-Specific Antibody-Drug Conjugates

Schöffski,

Wang,

Schöffski

et al. 2023

Oncol Res Treat

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Background: Topoisomerase I is an enzyme that plays a crucial part in DNA replication and transcription by the relaxation of supercoiled double-stranded DNA. Topoisomerase I inhibitors bind to the topoisomerase I cleavage complex, thereby stabilizing it and preventing the religation of the DNA strands, leading to DNA damage, cell cycle arrest, and apoptosis. Various topoisomerase I inhibitors have been evaluated in solid tumors, and irinotecan and topotecan have been approved for the treatment of epithelial malignancies. None of them have been approved for sarcoma, a diverse group of rare solid tumors with an unmet need for effective treatments. Summary: Topoisomerase I inhibitors have been evaluated in preclinical studies as single agents or in combination in solid tumors, some of which have included sarcomas where activity was observed. Clinical trials evaluating topoisomerase I inhibitors for the treatment of sarcoma have shown limited efficacy as monotherapy. In combination with other cytotoxic agents, topoisomerase I inhibitors have become part of clinical routine in selected sarcoma subtypes. Regimens such as irinotecan/vincristine/temozolomide are used in relapsed rhabdomyosarcoma, irinotecan/temozolomide and vincristine/topotecan/cyclophosphamide are commonly given in refractory Ewing sarcoma, and topotecan/carboplatin showed some activity in advanced soft tissue sarcoma. This review provides an overview of key studies with topoisomerase I inhibitors for the treatment of sarcoma. Topoisomerase I inhibitors are currently also being assessed as “payloads” for antibody-drug conjugates (ADCs), allowing for the targeting of specific antigen-expressing tumor cells and the delivery of the inhibitor directly to the tumor cells with the potential of enhancing therapeutic efficacy while minimizing systemic toxicity. Here, we also provide a brief overview on topoisomerase I-ADCs. Key Message: Topoisomerase I inhibitors are an important component of some systemic therapies for selected sarcomas and have potent cytotoxic properties and pharmacological characteristics that make them relevant candidates as payloads for the development of sarcoma-specific ADCs. ADCs are antibody-based targeted agents allowing for efficient and specific delivery of a given drug to the tumor cell. Topoisomerase I-ADCs are a novel targeted delivery approach which may have the potential to improve the therapeutic index of topoisomerase I inhibitors in the treatment of sarcoma and warrants investigation in a broad variety of mesenchymal malignancies.

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“…Genus Glycyrrhiza is a traditional Chinese herbal medicine. In last decades, increasing studies have reported the promising perspective of natural drugs in treating human diseases (Butnariu et al., 2023; Zafar et al., 2023). Isoliquiritigenin (2′, 4′, 4′‐trihydroxychalcone, ISL) is a flavonoid with a chalcone structure detached from licorice roots (Guo et al., 2023; Peng et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin attenuates neuroinflammation after subarachnoid hemorrhage through inhibition of NF‐κB‐mediated NLRP3 inflammasome activation

Wenfei,

Xiang,

Chen

et al. 2024

Chem Biol Drug Des

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Neuroinflammation contributes to neurological dysfunction in the patients who suffer from subarachnoid hemorrhage (SAH). Isoliquiritigenin (ISL) is a bioactive component extracted from Genus Glycyrrhiza. This work is to investigate whether ISL ameliorates neuroinflammation after SAH. In this study, intravascular perforation of male Sprague–Dawley rats was used to establish a SAH model. ISL was administered by intraperitoneal injection 6 h after SAH in rats. The mortality, SAH grade, neurological score, brain water content, and blood–brain barrier (BBB) permeability were examined at 24 h after the treatment. Expressions of tumor necrosis factor‐α, interleukin‐6, Iba‐1, and MPO were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). Besides, the expression levels of NF‐κB p65 and NLRP3, ASC, caspase‐1, IL‐1β, and IL‐18 were analyzed by western blot. The experimental data suggested that ISL treatment could ameliorate neurological impairment, attenuate brain edema, and ameliorate BBB injury after SAH in rats. ISL treatment repressed the expression of proinflammatory cytokines TNF‐α and IL‐6, and meanwhile inhibited the expression of Iba‐1 and MPO. ISL also repressed NF‐κB p65 expression as well as the transport from the cytoplasm to the nucleus. In addition, ISL significantly suppressed the expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, caspase‐1, IL‐1β, and IL‐18. These findings suggest that ISL inactivates NLRP3 pathway by inhibiting NF‐κB p65 translocation, thereby repressing the neuroinflammation after SAH, and it is a potential drug for the treatment of SAH.

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New insights into the anticancer therapeutic potential of maytansine and its derivatives

Cited by 13 publications

References 174 publications

CD7 Nanobody-Based Immuno-Nanotoxin for Targeted Treatment of T-Cell Acute Lymphoblastic Leukemia

CD7 Nanobody-Based Immuno-Nanotoxin for Targeted Treatment of T-Cell Acute Lymphoblastic Leukemia

Current Role of Topoisomerase I Inhibitors for the Treatment of Mesenchymal Malignancies and Their Potential Future Use as Payload of Sarcoma-Specific Antibody-Drug Conjugates

Isoliquiritigenin attenuates neuroinflammation after subarachnoid hemorrhage through inhibition of NF‐κB‐mediated NLRP3 inflammasome activation

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