Optimizing First-Line Treatment Options for Patients with Advanced NSCLC

Wakelee, Heather A.; Belani, Chandra P.

doi:10.1634/theoncologist.10-90003-1

Cited by 76 publications

(48 citation statements)

References 34 publications

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“…However, standard platinum-based combined chemotherapy is not sufficient for disease eradication (17). Recently, lung cancer treatment strategies have become refined through the development of molecular markers and molecularly targeted agents.…”

Section: Discussionmentioning

confidence: 99%

EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Sakairi

Nakajima

Yasufuku

et al. 2010

Clinical Cancer Research

145

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Purpose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non-small cell lung cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ALK-positive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic characteristics of ALK-positive lung cancer were also analyzed.Experimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node metastases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was determined using immunohistochemistry, and ALK gene rearrangements were further examined to verify the translocation between ALK and partner genes using fluorescent in situ hybridization and reverse transcription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants.Results: One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule-associated protein-like 4-ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histology and possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more likely to have smaller primary tumors (P < 0.05), to occur at a younger age (<60 years; P < 0.05), and to occur in never/light smokers (smoking index < 400; P < 0.01). Mucin production was frequently observed in ALK-positive adenocarcinomas (29.4%; P < 0.01).Conclusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC.Clin Cancer Res; 16(20); 4938-45. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Sakairi

Nakajima

Yasufuku

et al. 2010

Clinical Cancer Research

145

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“…4 Gene therapy approaches in the clinic are most likely to be undertaken in combination with chemotherapy. 20 Both cisplatin and etoposide are used to treat a large variety of tumor types, including osteosarcoma and NSCLC, 21,22 and for this reason we determined if Ad-Rybp would enhance the cytotoxic effects of these chemotherapeutic drugs. Ad-Rybp infection of U2OS cells increased the cytotoxicity of etoposide (Figure 5a), with marginal, if any, enhancement of cisplatin cytotoxicity (Figure 5b).…”

Section: Discussionmentioning

confidence: 99%

“…For the treatment of osteosarcoma and NSCLC, platinum based-therapies, such as cisplatin, are often used as a first-line treatment. 21,22 Platinum compounds are either used alone or in combination with other non-platinum agents, including etoposide. 21,22 As such, we tested if Ad-Rybp would sensitize U20S or A549 cells to the cytotoxic effects of cisplatin or etoposide treatments.…”

Section: Ad-rybp Induces Apoptosismentioning

confidence: 99%

Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

Novak

Phillips

2008

Cancer Gene Ther

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Previous work demonstrated that exogenous expression of Rybp (Ring 1 YY1-binding protein or DEDAF) kills tumor but not nontransformed cells. This tumor-preferential killing activity could be exploited in a gene therapy approach to treat cancer. To test the potential of viral-mediated delivery of Rybp as an anticancer treatment, we generated an adenovirus expressing Rybp (Ad-Rybp). Infection with Ad-Rybp inhibits the proliferation of a range of tumor cell lines, but has no effect on normal cell types. This inhibition of proliferation is the result of the induction of apoptosis, consistent with reports that Rybp regulates apoptosis. Combined Ad-Rybp infection and etoposide treatment resulted in an additive cytotoxic effect in the osteosarcoma cell line U20S. Furthermore, Ad-Rybp infection synergistically cooperates with the death receptor ligand, tumor necrosis factor-a, in the induction of apoptosis. These results suggest that Ad-Rybp may have clinical applicability, either alone or in combination with other agents for the treatment of cancer.

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“…Clinically, VC appears to have large interindividual variability in its pharmacokinetic effects. The overall response rate is <50% [1], and inherited differences in the metabolism and disposition of drugs, and genetic polymorphisms in the targets of drug therapy (such as receptors) may significantly affect the efficacy of medications.…”

Section: Introductionmentioning

confidence: 99%

MDR1 Single Nucleotide Polymorphisms Predict Response to Vinorelbine-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Pan

Han

et al. 2007

Respiration

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Background: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. Objectives: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). Methods: We determined the genotypes of CYP3A5(*3), MDR1 (2677G→T at exon 21 and 3435C→T at exon 26 and their haplotypes) and COX-2 (–1195G→A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The χ² test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. Results: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435-2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (–1195G) is likely to result in a better response to vinorelbine (nonsignificant). Conclusions: Our findings suggest that MDR1 2677G→T/A and 3435C→T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients.

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Optimizing First-Line Treatment Options for Patients with Advanced NSCLC

Cited by 76 publications

References 34 publications

EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

MDR1 Single Nucleotide Polymorphisms Predict Response to Vinorelbine-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

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