Chemotherapy and targeted therapy in the management of cervical cancer

Kumar, Lalit; Harish, P; Malik, Prabhat Singh; Khurana, Sachin

doi:10.1016/j.currproblcancer.2018.01.016

Cited by 140 publications

(90 citation statements)

References 35 publications

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“…4,5 Therefore, searching a new therapeutic target of cervical cancer is critically needed to enhance the sensitivity of chemoradiotherapy, reduce recurrence and metastasis after chemotherapy and sequentially improve the disease prognosis. [6][7][8] Maternal embryonic leucine zipper kinase (MELK) is a kind of cell cycle dependent conserved serine/threonine protein kinase, at chromosome 9p13.2. Unlike other members of the family, MELK is not related to cellular energy metabolism balance.…”

Section: Introductionmentioning

confidence: 99%

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

Wang

Shen

et al. 2018

Cancer Medicine

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Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore the expression of MELK in cervical cancer, as well as its effects on the proliferation, apoptosis, DNA damage repair on cervical cancer cell line in vitro and to provide novel ideas for further improving the clinical efficacy of cervical cancer. Immunohistochemistry, Western blot, RT‐qPCR, CCK8, and immunofluorescence techniques were used to detect the expression of MELK in cervical cancer tissues, paracancerous tissues, and cervical cancer cell lines. Several cervical cancer cell lines were treated with MELK knockdown by siRNA and MELK selective inhibitor OTSSP167. The effects on proliferation, apoptosis, and colony formation capacity, and tumor cell DNA damage repair‐related factor were detected in cell lines. Our data showed that the high expression rate of MELK in cervical cancer patients was 56.92%. MELK expression in cervical cancer samples was significantly higher than that in paraneoplastic tissues. Highly expressed MELK correlated with the cervical histopathological grading and greatly increased with the cervical histopathological grading, from normal cervix and cervical intraepithelial neoplasia to cervical cancer. Moreover, the abnormal expression of MELK was related to cervical cancer metastasis at early stage. The knockdown of MELK with siRNA and OTSSP167 had strong inhibition effects on the proliferation, apoptosis, and colony formation of cervical cancer cells. MELK knockdown could also aggravate the DNA damage of cervical cancer cells possibly by homologous recombination repair pathway. Therefore, MELK may be a predicting marker of poor prognosis of cervical cancer and may also be a new therapeutic target for cervical cancer, providing ideas for improving the therapeutic effect of cervical cancer.

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Section: Introductionmentioning

confidence: 99%

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

Wang

Shen

et al. 2018

Cancer Medicine

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“…Cervical cancer is a major cause of mortality and morbidity in women worldwide, especially in low and middle-income countries [1,2]. In the presence of metastases, the prognosis of cervical cancer is poor, and the standard treatment is palliative chemotherapy until disease progression or unacceptable toxicity [3,4]. The most used regimens for first-line treatment are platinum combinations supported mainly by the phase III gynecologic oncology group (GOG)-169 [6], GOG-179 [7], and GOG-204 trials [8].…”

Section: Discussionmentioning

confidence: 99%

“…In the presence of distant metastases, the prognosis is poor, and, in these cases, the standard management is palliative cytotoxic chemotherapy with or without bevacizumab [3,4]. Oligometastatic (i.e., limited metastatic) disease seems to have a better prognosis than a disseminated disease, especially if patients receive a multimodal ablative approach that includes radiotherapy or surgery, with or without chemotherapy [5].…”

Section: Introductionmentioning

confidence: 99%

Concurrent Chemoradiation for Mediastinal Oligometastases From Cervical Cancer: A Potentially Curative Treatment

Bonilla

Laguado

Quintero

2020

Cureus

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“…(19) Concurrent chemo-radiation therapy is the current standard of care for patients with locally advanced cervical cancer, and targeted therapies using tyrosine kinase inhibitors have been consistently attempted to manage metastatic or recurrent patients with low response rates. (20) Even though this disease is generally preventable, the overall prognosis for women with metastatic or recurrent types is poor. (21) Here, we shed light on the in vitro anti-cancer activity of NC for treatment of human cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

A new insight into the apoptotic effect of nitidine chloride targeting Checkpoint kinase 2 in human cervical cancer <i>in vitro</i>

Kwon

Kim

Ahn

et al. 2019

J. Clin. Biochem. Nutr.

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Nitidine chloride (NC), a natural, bioactive, phytochemical alkaloid derived from the roots of Zanthoxylum nitidum, has been reported to exhibit anti tumor activity against various types of cancer. However, the potential therapeutic role of NC in human cervical cancer has not yet been studied. We are the first to report that NC acts as a potential apoptosis inducing agent for human cervical cancer in vitro. NC treatment of human cervical cancer cell lines induced caspase mediated apoptosis, thereby reducing cell viability. Phospho kinase proteome profiling using a human phospho kinase array revealed that NC treatment phosphorylated Checkpoint kinase 2 (Chk2) at Thr68, which activates Chk2 in both cell lines. We also found that NC significantly affected the p53/Bim signaling axis, which was accompanied by mitochondrial membrane depo larization and cytochrome c release from the mitochondria into the cytosol. In addition, NC profoundly increased phosphorylation of the histone variant H2AX at Ser139, a typical marker of DNA damage. Taken together, these results provide in vitro evidence that NC can increase Chk2 activation, thereby acting as an attrac tive cell death inducer for treatment of human cervical cancer.

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Chemotherapy and targeted therapy in the management of cervical cancer

Cited by 140 publications

References 35 publications

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

Concurrent Chemoradiation for Mediastinal Oligometastases From Cervical Cancer: A Potentially Curative Treatment

A new insight into the apoptotic effect of nitidine chloride targeting Checkpoint kinase 2 in human cervical cancer <i>in vitro</i>

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