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MicroRNAs associated with tumour migration, invasion and angiogenic properties in A549 and SK-Lu1 human lung adenocarcinoma cells

Ho CS, Yap SH, Phuah NH, In LL, Hasima N

Lung Cancer, 2014 Feb;83(2):154-62.
PMID: 24360396 DOI: 10.1016/j.lungcan.2013.11.024

Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.
Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study

Wu YL, Kim JH, Park K, Zaatar A, Klingelschmitt G, Ng C

Lung Cancer, 2012 Aug;77(2):339-45.
PMID: 22494567 DOI: 10.1016/j.lungcan.2012.03.012

Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those observed in the overall SATURN population. Maintenance treatment with erlotinib appears to be a useful option for the management of Asian patients with advanced NSCLC without progression after first-line chemotherapy.
Successful pregnancy with epidermal growth factor receptor tyrosine kinase inhibitor treatment of metastatic lung adenocarcinoma presenting with respiratory failure

Lee CH, Liam CK, Pang YK, Chua KT, Lim BK, Lai NL

Lung Cancer, 2011 Nov;74(2):349-51.
PMID: 21920622 DOI: 10.1016/j.lungcan.2011.08.008

We report a woman presenting with respiratory failure due to a right-sided pleural effusion, lung metastases and lymphangitis carcinomatosis from advanced lung adenocarcinoma in the third trimester of pregnancy, who showed good response to EGFR tyrosine kinase inhibitor.
Changes in the distribution of lung cancer cell types and patient demography in a developing multiracial Asian country: experience of a university teaching hospital

Liam CK, Pang YK, Leow CH, Poosparajah S, Menon A

Lung Cancer, 2006 Jul;53(1):23-30.
PMID: 16690159

A comparison of patients with lung cancer diagnosed at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia from October 1991 to September 1999 with another group of lung cancer patients diagnosed at the same hospital during an earlier period of 1967-1976 was undertaken to determine whether there had been a change in the distribution of lung cancer cell types and patient demography. The number of histologically and/or cytologically proven lung cancer cases was 583 from October 1991 to September 1999 and 278 from 1967 to 1976. The mean (S.D.) age of the patients during the period 1991-1999, 60.1 (12.0) years was similar to that of patients during the period 1967-1976, 60.3 (12.2) years. There was no shift of the peak age distribution of lung cancer (i.e., the 7th decade) between the two periods. In the recent period, the percentage of patients with adenocarcinoma had increased significantly to 43.2% from 25.2% while that of large cell carcinoma had decreased to 3.3% from 11.9%. The percentages of patients with squamous cell carcinoma (SCC) and small cell lung cancer remained stable. In the period 1967-1976, SCC was the commonest cell type in men and in smokers while adenocarcinoma was the commonest cell type in women and in never smokers. In the period 1991-1999, adenocarcinoma was the commonest cell type in both men and women as well as in smokers and never smokers.
Fulltext Molecular testing for advanced non-small cell lung cancer in Malaysia: Consensus statement from the College of Pathologists, Academy of Medicine Malaysia, the Malaysian Thoracic Society, and the Malaysian Oncological Society

Rajadurai P, Cheah PL, How SH, Liam CK, Annuar MAA, Omar N, et al.

Lung Cancer, 2019 10;136:65-73.
PMID: 31446227 DOI: 10.1016/j.lungcan.2019.08.005

In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.
Clinical utility of a blood-based EGFR mutation test in patients receiving first-line erlotinib therapy in the ENSURE, FASTACT-2, and ASPIRATION studies

Wu YL, Lee V, Liam CK, Lu S, Park K, Srimuninnimit V, et al.

Lung Cancer, 2018 12;126:1-8.
PMID: 30527172 DOI: 10.1016/j.lungcan.2018.10.004

OBJECTIVE: Patients with advanced non-small-cell lung cancer (NSCLC) with an adenocarcinoma component are recommended to undergo epidermal growth factor receptor (EGFR) mutation testing when being considered for EGFR targeted therapy. We conducted an exploratory analysis to inform the clinical utility of EGFR mutation testing in blood cell-free DNA using the cobas®EGFR Mutation Test v2.
MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.
RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.
CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.
Short communication: Diagnosis of lung cancer increases during the annual southeast Asian haze periods

Hassan A, Latif MT, Soo CI, Faisal AH, Roslina AM, Andrea YLB, et al.

Lung Cancer, 2017 11;113:1-3.
PMID: 29110834 DOI: 10.1016/j.lungcan.2017.08.025

There have been few but timely studies examining the role of air pollution in lung cancer and survival. The Southeast Asia haze is a geopolitical problem that has occurred annually since 1997 in countries such as Malaysia, Singapore and Indonesia. To date, there has been no study examining the impact of the annual haze in the presentation of lung cancer. Data on all lung cancers and respiratory admissions to Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2010 to 31th October 2015 were retrospectively collected and categorized as presentation during the haze and non-haze periods defined by the Department of Environment Malaysia. We report a lung cancer incidence rate per week of 4.5 cases during the haze compared to 1.8 cases during the non-haze period (p<0.01). The median survival for subjects presenting during the haze was 5.2 months compared to 8.1 months for the non-haze period (p<0.05). The majority of subjects diagnosed during the haze period initially presented with acute symptoms. Although this study could not suggest a cause and effect relationship of the annual haze with the incidence of lung cancer, this is the first study reporting a local air pollution-related modifiable determinant contributing to the increase in presentation of lung cancer in Southeast Asia.
Corrigendum to "Short communication: Diagnosis of lung cancer increases during the annual southeast Asian haze periods" [Lung Cancer 113 (2017) 1-3]

Hassan A, Latif MT, Soo CI, Faisal AH, Roslina AM, Ban Andrea YL, et al.

Lung Cancer, 2021 Apr;154:229.
PMID: 33678457 DOI: 10.1016/j.lungcan.2021.02.024
Fulltext A unique small cell lung carcinoma disease progression model shows progressive accumulation of cancer stem cell properties and CD44 as a potential diagnostic marker

Heng WS, Pore M, Meijer C, Hiltermann TJN, Cheah SC, Gosens R, et al.

Lung Cancer, 2021 04;154:13-22.
PMID: 33607458 DOI: 10.1016/j.lungcan.2021.02.002

OBJECTIVES: Cancer stem cells (CSCs) have been implicated in disease progression of aggressive cancers including small cell lung carcinoma (SCLC). Here, we have examined the possible contribution of CSCs to SCLC progression and aggressiveness.
MATERIALS AND METHODS: GLC-14, GLC-16 and GLC-19 SCLC cell lines derived from one patient, representing increasing progressive stages of disease were used. CSC marker expressions was determined by RT-qPCR and western blotting analyses, and heterogeneity was studied by CSC marker expression by immunofluorescence microscopy and flow cytometry. Colony formation assays were used to assess stem cell properties and therapy sensitivity.
RESULTS: Increasing expression of stem cell markers MYC, SOX2 and particularly CD44 were found in association with advancing disease. Single and overlapping expression of these markers indicated the presence of different CSC populations. The accumulation of more homogeneous double- and triple-positive CSC populations evolved with disease progression. Functional characterization of CSC properties affirmed higher proficiency of colony forming ability and increased resistance to γ-irradiation in GLC-16 and GLC-19 compared to GLC-14. GLC-19 colony formation was significantly inhibited by a human anti-CD44 antibody.
CONCLUSION: The progressive increase of MYC, SOX2 and particularly CD44 expression that was accompanied with enhanced colony forming capacity and resistance in the in vitro GLC disease progression model, supports the potential clinical relevance of CSC populations in malignancy and disease relapse of SCLC.
Challenges and future direction of molecular research in air pollution-related lung cancers

Shahadin MS, Ab Mutalib NS, Latif MT, Greene CM, Hassan T

Lung Cancer, 2018 04;118:69-75.
PMID: 29572006 DOI: 10.1016/j.lungcan.2018.01.016

Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.