Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature

Vennepureddy, Adarsh; Atallah, Jean-Paul; Terjanian, Terenig

doi:10.14740/wjon950e

Cited by 18 publications

(18 citation statements)

References 27 publications

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“…* indicates p < 0.05 comparing resistant cell line with or without Ko143 to parental cell line with or without Ko143; # indicates p < 0.05 comparing a group with Ko143 to the corresponding cell line group without Ko143. (Vennepureddy et al, 2015), but the development of MDR in tumors remains a serious obstacle for successful treatment. In MDR-exhibiting NSCLC cells that acquire resistance to one drug often develop resistance to a range of other structurally and functionally unrelated anticancer agents, resulting in cancer recurrence, and even relapse or death (Osmani et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy is the predominant form of treatment for advanced NSCLC. Topotecan is one of the first-line drugs in treating NSCLC with a favorable side effect profile ( Vennepureddy et al, 2015 ), but the development of MDR in tumors remains a serious obstacle for successful treatment. In MDR-exhibiting NSCLC cells that acquire resistance to one drug often develop resistance to a range of other structurally and functionally unrelated anticancer agents, resulting in cancer recurrence, and even relapse or death ( Osmani et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Topotecan is currently approved by the US FDA for small cell lung cancer (SCLC) clinically first- and second-line therapies ( Spigel et al, 2013 ). It has shown to be efficacious in the treatment of NSCLC with a favorable side effect profile ( Vennepureddy et al, 2015 ). Several clinical trials demonstrated that either oral or IV single-agent topotecan can be used as a second-line therapy for patients with progressed or relapsed NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line

Lei

Teng

Zhang

et al. 2020

Front. Cell Dev. Biol.

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While topotecan (TPT) is a first- and second-line chemotherapeutic drug in treating lung cancer, the development of drug resistance in tumors still reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of topotecan resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in topotecan-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143. The NCI-H460/TPT10 cell line and its parental cell line can be useful for drug screening and developing targeted strategies to overcome ABCG2-mediated MDR in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line

Lei

Teng

Zhang

et al. 2020

Front. Cell Dev. Biol.

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“…It has been suggested that TPT has a good prospect as a first-or second-line treatment for progressed or relapsed NSCLC because of its high efficacy and favorable side effect profile (Vennepureddy et al, 2015). However, as TPT is FIGURE 3 | Effect of cabozantinib combined with topotecan on the expression of ABCG2 and topoisomerase I (TOP1).…”

Section: Discussionmentioning

confidence: 99%

Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model

Lei

Teng

Gupta

et al. 2021

Front. Cell Dev. Biol.

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Cabozantinib (CBZ) is a small molecule tyrosine kinase receptor inhibitor, which could also inhibit the ABCG2 transporter function. Therefore, CBZ could re-sensitize cancer cells that are resistant to ABCG2 substrate drugs including topotecan (TPT). However, its reversal effect against TPT resistance has not been tested in a TPT-induced resistant cancer model. In this study, a new TPT selected human non-small cell lung cancer (NSCLC)-resistant cell model NCI-H460/TPT10 with ABCG2 overexpression and its parental NCI-H460 cells were utilized to investigate the role of CBZ in drug resistance. The in vitro study showed that CBZ, at a non-toxic concentration, could re-sensitize NCI-H460/TPT10 cells to TPT by restoring intracellular TPT accumulation via inhibiting ABCG2 function. In addition, the increased cytotoxicity by co-administration of CBZ and TPT may be contributed by the synergistic effect on downregulating ABCG2 expression in NCI-H460/TPT10 cells. To further verify the applicability of the NCI-H460/TPT10 cell line to test multidrug resistance (MDR) reversal agents in vivo and to evaluate the in vivo efficacy of CBZ on reversing TPT resistance, a tumor xenograft mouse model was established by implanting NCI-H460 and NCI-H460/TPT10 into nude mice. The NCI-H460/TPT10 xenograft tumors treated with the combination of TPT and CBZ dramatically reduced in size compared to tumors treated with TPT or CBZ alone. The TPT-resistant phenotype of NCI-H460/TPT10 cell line and the reversal capability of CBZ in NCI-H460/TPT10 cells could be extended from in vitro cell model to in vivo xenograft model. Collectively, CBZ is considered to be a potential approach in overcoming ABCG2-mediated MDR in NSCLC. The established NCI-H460/TPT10 xenograft model could be a sound clinically relevant resource for future drug screening to eradicate ABCG2-mediated MDR in NSCLC.

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“…First, pemetrexed + cisplatin polychemotherapy started because this regimen combination was reported to be effective and well-tolerated in NSCLC patients with brain metastases (16). Then the patient was treated with topotecan, a Topoisomerase I inhibitor that previously showed encouraging results in the NSCLC treatment (17). Finally, the patient was prescribed with crizotinib.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics-Guided Personalized Prescription of Targeted Therapeutics for Metastatic ALK-Positive Lung Cancer Case Following Recurrence on ALK Inhibitors

Poddubskaya¹,

Bondarenko²,

Boroda

et al. 2019

Front. Oncol.

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Non-small cell lung carcinoma (NSCLC) is the major cause of cancer-associated mortality. Identification of rearrangements in anaplastic lymphoma kinase (ALK) gene is an effective instrument for more effective targeted therapy of NSCLC using ALK inhibitors dramatically raising progression-free survival in the ALK-mutated group of patients. However, the tumors frequently develop resistance to ALK inhibitors. We describe here a case of 48 y.o. male patient with ALK-positive NSCLC who was clinically managed for 6.5 years from the diagnosis. The tumor was surgically resected, but 8 months later multiple brain metastases were discovered. The patient started receiving platinum-based chemotherapy and then was enrolled in a clinical trial of second-generation ALK inhibitor ceritinib, which resulted in a 21 months stabilization. Following disease relapse, the patient was successfully managed for 33 months with different lines of chemo- and local ablative therapies. Chemotherapy regimens, including off-label combination of crizotinib + bevacizumab + docetaxel, were selected using the cancer transcriptome data-guided bioinformatical decision support system Oncobox. These therapies led to additional stabilization for 22 months. Survival of our patient after developing resistance to ALK inhibitor was longer for 16 months than previously reported average survival for such cases. This case shows that transcriptomic-guided sequential personalized prescription of targeted therapies can be effective in terms of survival and quality of life in ALK-mutated NSCLC.

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Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature

Cited by 18 publications

References 27 publications

Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line

Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line

Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model

Transcriptomics-Guided Personalized Prescription of Targeted Therapeutics for Metastatic ALK-Positive Lung Cancer Case Following Recurrence on ALK Inhibitors

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