Lung cancer is a type of cancer that develops in the tissues of the lungs, usually in cells lining the air passages.  It starts when the cells become abnormal and grow uncontrollably, eventually spreading to other parts of the body. There are two main types of lung cancer – non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with the former constituting about 80 – 85% of lung cancers. 
National Lung Cancer Profiling Programme
In Singapore, lung cancer is the second most common cancer in males and third most common in females .
The Lung Cancer Consortium Singapore (LCCS) was established to collect biospecimens*, lifestyle questionnaires and clinical data. In LCCS, data managers and coordinators who are specially trained in lung cancer research approach patients and explain the need and importance of data collection to them.
To date, LCCS has obtained clinical data from about 3600 patients, and collated around 3000 lifestyle questionnaires and about 2300 biospecimens. They have also organised meetings and workshops to encourage the collaborations between healthcare professionals in the treatment of lung cancer.
A national lung cancer profiling programme will be carried out by the researchers from the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH). Under the auspices of LCCS, the detailed molecular profiling of lung cancer patients’ tumour cells will start in January 2017, where LCCS will provide a tissue and clinical data bank to support lung cancer research. At present, the targeted therapy is available only for some NSCLC mutations which are profiled. In fact, there are several emerging subgroups that may harbour rare targetable gene mutations. With the increasing number of targetable mutations, there is an increasing need for comprehensive and longitudinal evaluation.
This molecular profiling would be a significant study for further understanding about the disease and exploration of potential novel treatment options for patients.
*The biospecimens here mainly refer to patients’ blood samples and tissues.
Novel Treatments in Lung Cancer
At a media briefing held by NCCS, Dr Toh Chee Keong and Dr Daniel Tan, both Senior Consultant Medical Oncologists at NCCS, explained that their research efforts were about helping doctors understand local patient profiles better. Dr Tan expressed his hope in obtaining meaningful data through the lung cancer profiling programme where the molecular profiling effort will be led by Dr Tony Lim, Senior Consultant from the Department of Anatomical Pathology, Singapore General Hospital.
Lung cancer research is essential in Singapore as the lung cancer prevalence in Asia, including Singapore, is different from that of the West. According to data from NCCS and LCCS, from 1999 to 2006, cancer patients who are non-smokers have increased from 31% to almost 50% of the total number of cancer patients. The reason as to why non-smokers get lung cancer is still unknown. Data from LCCS also showed that the EGFR (Epidermal Growth Factor Receptor) mutation, which is more common in non-smoker patients, is much higher in Singapore (43.6%) compared to the United States (below 15%) . Therefore, lung cancer research is specifically needed in Singapore to address these unknowns.
The existing treatment options for NSCLC patients include surgery, chemotherapy, radiotherapy, among others. In recent years, new treatment options that are tailored to a tumour’s molecular profile have been introduced. Immunotherapy, which harnesses the patient’s immune system to attack cancer cells inside the body, is fast becoming popular among cancer treatment options. It is a unique form of treatment, as it targets the immune system rather than the tumour itself. Examples of immunotherapy for the treatment of locally advanced or metastatic NSCLC include Nivolumab and Pembrolizumab. Both Pembrolizumab and Nivolumab were approved by the Health Sciences Authority of Singapore (HSA) in 2016, and they work by inhibiting the PD-1 proteins on cells that block the body’s immune system from attacking tumour cells. 
A keynote study showed that Pembrolizumab increases the overall survival rate among NSCLC patients with PD-L1-expressing tumour cells compared to chemotherapy. A 2 mg/kg dose of Pembrolizumab resulted in a 29% improvement in the overall survival, compared to docetaxel (chemotherapy). The median overall survival rate for a 2 mg/kg dose of Pembrolizumab was 10.4 months (95% CI, 9.4-11.9), which was higher compared to 8.5 months for Docetaxel (95% CI, 7.5-9.8). 
At the media briefing on the national lung cancer profiling programme, Mr Khoo Lay Tit, 53, a Stage IV lung cancer patient, shared his treatment journey with APBN. While on the immunotherapy drug, Pembrolizumab, he said that his tumour had shrunk and there were no side effects so far. He quit smoking after his disease, and is optimistic about his treatment journey and grateful for the support and love from his family.
II. PD-L1 expression
In the early 1990s, a biologist in Japan discovered a protein named programmed death receptor-1 (PD-1), which is expressed in dying T-cells. T-cells, a type of white blood cells, are responsible for attacking the antigens they recognise as ‘foreign’ to the body, and in turn, triggering an appropriate immune response. Following the discovery, researchers began to explore lung cancer treatments by using anti-PD-1 antibodies, and a few major drug companies are currently developing anti-PD-1 therapies. 
Studies that used a protein-based biomarker as therapy – the PD-L1 expression, have been useful to stratify patients that respond to immunotherapy drugs. Programmed death-ligand 1 (PD-L1) is a protein expressed on many types of cells, including some cancer cells. The interaction between the two proteins, PD-L1 and PD-1, is vital in keeping the immune system in check, preventing the body from attacking its own cells when there is an inflammation or infection . When the PD-L1 is overexpressed by cancerous tumours, they will escape detection by cytotoxic T-cells – a type of cancer-killing immune cell – preventing the destruction of tumours. In other words, unnaturally high levels of PD-L1, or an overexpression of PD-L1, may indicate an inhibited immune response caused by the tumour cells. This PD-L1 overexpression is currently under investigation for potential use in addressing targeted treatment for cancer patients [8-11].
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- Herbst et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016; 387(10027): 1540-50.
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- Chen DS et al. Molecular Pathway: Next-Generation Immunotherapy – Inhibiting Programmed Death-Ligand 1 and Programmed Death-1. Clin Cancer Res. 2012. 18(24): 6580-7.
- Mellman I et al. Cancer Immunotherapy Comes of Age. Nature. 2011. 480(7378):480-489.
- Zhang Y, et al. Protein Expression of Programmed Death 1 Ligand 1 and Ligand 2 Independently Predict Poor Prognosis in Surgically Resected Lung Adenocarcinoma. OncoTargets and Therapy. 2014. 7:567–573.
- Chen Y-B, et al. Clinical Significance of Programmed Death-1 Ligand-1 Expression in Patients with Non-Small Cell Lung Cancer: A 5-Year-Follow-Up Study. Tumori. 2012. 98:751–755.