Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy

Son, Sangyoung; Shin, Sol; Rao, N. Vijayakameswara; Um, Wooram; Jeon, Jueun; Ko, Hyewon; Deepagan, V. G.; Kwon, Seunglee; Lee, Jun Young; Park, Jae Hyung

doi:10.1016/j.ijbiomac.2017.10.113

Cited by 53 publications

(39 citation statements)

References 28 publications

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“…Previous studies have linked TROP2 to increased tumor growth and demonstrated TROP2 to be a candidate tumor prognostic marker in various tumors. TROP2 is found to be overexpressed in the majority of human epithelial cancers, including pancreatic cancer, gastric cancer, lung cancer, ovarian cancer, and colorectal cancers (10,14,32). Chen et al (33) investigated the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with gallbladder cancer (GBC) and demonstrated that increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

Nijiati

Gao

et al. 2018

Mol Med Report

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Human trophoblast cell surface antigen 2 (TROP2) has been noted to serve an important role in the proliferation and migration of various types of human cancers. However, the potential role and the molecular mechanisms of TROP2 in osteosarcoma (OS) remain largely unclear. In the present study, high expression of TROP2 in human OS tissues and cell lines was observed. Overexpression of TROP2 promoted the proliferation and migration of OS cell lines, while TROP2 knockdown markedly decreased cell growth and migration. Furthermore, it was revealed that TROP2 overexpression significantly activated the phosphoinositide 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway. Collectively, these results suggested that TROP2 may promote OS cell proliferation and migration via PI3K/AKT signaling and may serve as a novel treatment target for OS.

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Section: Discussionmentioning

confidence: 99%

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

Nijiati

Gao

et al. 2018

Mol Med Report

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“…This section focuses on two anti-TROP-2 ADCs that have been studied clinically, sacituzumab govitecan, using the topoisomerase inhibitor, SN-38 (an irinotecan metabolite) [ 66 , 99 – 107 ], and another agent, RN927C, coupled to a derivative of the microtubule inhibitor, auristatin [ 108 , 109 ]. Other TROP-2-targeted therapeutics have been described preclinically, one using a nanoparticle (carboxymethyl dextran) carrier linked with doxorubicin, which has activity in the MDA-MB-231 breast cancer cell line representative of TNBC [ 110 ], and another, utilizing doxorubicin conjugated to an anti-TROP-2 Fab, with activity in vitro and in vivo against pancreatic cancer [ 111 ].…”

Section: Antibody-drug Conjugates (Adcs)mentioning

confidence: 99%

The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target

2018

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TROP-2 is a glycoprotein first described as a surface marker of trophoblast cells, but subsequently shown to be increased in many solid cancers, with lower expression in certain normal tissues. It regulates cancer growth, invasion and spread by several signaling pathways, and has a role in stem cell biology and other diseases. This review summarizes TROP-2's properties, especially in cancer, and particularly its role as a target for antibody-drug conjugates (ADC) or immunotherapy. When the irinotecan metabolite, SN-38, is conjugated to a humanized anti-TROP-2 antibody (sacituzumab govitecan), it shows potent broad anticancer activity in human cancer xenografts and in patients with advanced triple-negative breast, non-small cell and small-cell lung, as well as urothelial cancers.

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“…For instance, the combination of nanoparticles with antibodies introduces maximum advantages with higher safety and selectivity than each carrier alone ( fig. 5) [47][48][49][50]. This combination depends on the capability of nanoparticles to carry a large number of toxic drugs and the ability of antibodies to provide these drugs specifically into the site of action through the endocytosis mechanism [47].…”

Section: Fig 5: a Combination Of Nanoparticle With Antibodies And Otmentioning

confidence: 99%

The Impact of New Targeting Methods in the Cancer Therapy

2019

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Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later have been also discussed. PubMed and Science Direct were the main search engines that have been used as information sources to prepare this review. Articles related to cancer targeting system, active and passive processes, current nanoparticles, antibody carriers, and current novel cancer carriers were used as sources in this review. Important points from many references published in the last decade (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) were selected and included. Several targeting methods were introduced to enhance the efficacy and tolerability of the toxic drug by active and passive processes, but there is still no conclusive carrier without certain drawbacks. A combination of targeting methods probably shows the most appropriate choice for increasing selectivity and safety of anticancer drugs via reducing the concentration of carriers used. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s

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Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy

Cited by 53 publications

References 28 publications

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target

The Impact of New Targeting Methods in the Cancer Therapy

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