Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC

Chang, Alex Y.

doi:10.1016/j.lungcan.2010.08.022

Cited by 382 publications

(325 citation statements)

References 71 publications

(100 reference statements)

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“…38 Thus, the assessment of new and reliable molecular markers can help clinicians to predict the response to conventional therapies and improve therapeutic strategies. 14 In this work, we present evidence that CCDC6 protein is down regulated in lung tumors, thereby enhancing tumor aggressiveness and reducing sensitivity to DNA damaging agents, such as cisplatinum.…”

Section: Discussionmentioning

confidence: 99%

New therapeutic perspectives in CCDC6 deficient lung cancer cells

Morra

Luise

Visconti

et al. 2014

Intl Journal of Cancer

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Non-small cell lung cancer (NSCLC) is the main cause of cancer-related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled-coildomain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index <1. Finally, CCDC6 is expressed at low levels in about 30% of the NSCL tumors we analyzed by TMA immunostaining. The weak CCDC6 protein staining is significatively correlated with the presence of lymph node metastasis (p 0.02) and negatively correlated to the disease free survival (p 0.01) and the overall survival (p 0.05). Collectively, the data indicate that CCDC6 levels provide valuable insight for OS. CCDC6 could represent a predictive biomarker of resistance to conventional single mode therapy and yield insight on tumor sensitivity to PARP inhibitors in NSCLC.

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Section: Discussionmentioning

confidence: 99%

New therapeutic perspectives in CCDC6 deficient lung cancer cells

Morra

Luise

Visconti

et al. 2014

Intl Journal of Cancer

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“…However, the therapeutic results in some patients with advanced NSCLC are unsatisfying as for intrinsic or acquired chemoresistance, and identification of novel molecular targets for chemosensitization of human LAD will, therefore, have enormous clinical applications (20). cDNA microarray analysis showed that Bcl-xL was significantly upregulated in SPC-A1/DTX cells.…”

Section: Discussionmentioning

confidence: 99%

Let-7c Governs the Acquisition of Chemo- or Radioresistance and Epithelial-to-Mesenchymal Transition Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma

Cui

Huang

Chen

et al. 2013

Molecular Cancer Research

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MicroRNA (miRNA) expression and functions have been reported to contribute to phenotypic features of tumor cells. Although targets and functional roles for many miRNAs have been described in lung adenocarcinoma (LAD), their pathophysiologic roles in phenotypes of chemoresistant LAD cells are still largely unclear. Previously, docetaxel (DTX)-resistant LAD cell lines (SPC-A1/DTX and H1299/DTX) were established by our laboratory and displayed chemo-or radioresistance and mesenchymal features with enhanced invasiveness and motility. Unbiased miRNA profiling indicated that let-7c (MIRLET7C) was significantly downregulated in SPC-A1/DTX cells. Ectopic let-7c expression increased the in vitro and in vivo chemo-or radiosensitivity of DTX-resistant LAD cells through enhanced apoptosis, reversal of epithelial-tomesenchymal phenotypes, and inhibition of in vivo metastatic potential via inactivation of Akt phosphorylation, whereas a let-7c inhibitor decreased the chemo

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“…In clinical practice, the chemotherapy response is variable among individuals. About one-third of NSCLC patients achieve complete remission (CR) or a partial response (PR) following the standard first-line chemotherapy, while another one-third show stable disease (SD) and progressive disease (PD), respectively (Chang, 2011). Thus, the identification of predictive markers of the response to chemotherapy is an urgent issue.…”

Section: Introductionmentioning

confidence: 99%

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

Yanagita

Nagashio²,

Ryuge³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. Materials and Methods: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. Results: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinumbased chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). Conclusions: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.

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Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC

Cited by 382 publications

References 71 publications

New therapeutic perspectives in CCDC6 deficient lung cancer cells

New therapeutic perspectives in CCDC6 deficient lung cancer cells

Let-7c Governs the Acquisition of Chemo- or Radioresistance and Epithelial-to-Mesenchymal Transition Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

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