Table of Contents

I. Introduction
II. Risk Factors for Lung Cancer
III. Diagnosis of Lung Cancer
IV. Types of Lung Cancer
A. Small Cell Lung Cancer
B. Non-Small Cell Lung Cancer
V. Drugs used for Hypertension, Angiotensin Converting Enzyme Inhibitors (ACEIs), at Increased Risk of Lung Cancer
VI. Treatment Advances
A. Tecentriq in Combination with Avastin and Chemotherapy
B. BRAF inhibitors for the treatment of non-small cell lung cancer
VII. Interventional Pulmonology for the Diagnosis and Treatment of Lung Cance

Lung Cancer Identified as One of the Most Common Malignancy Globally

Lung cancer is considered the leading cause of death among men and the second cause of death among women globally. It claims more lives than the ovarian, breast and colon cancers combined mainly because of the advanced stage of the disease at the time of diagnosis.

The inhaling of carcinogens with smoking is identified as one of the major risk factors for the development of lung cancer. As smoking can damage the lung tissue, which the body generally repairs initially, but the continued long-term exposure damages the lining of the lungs resulting in the development of cancer. Some of the other risk factors include exposure to chemicals or toxins over a long period of time which can also make changes and damages to the lung cells. Also, according to the Cancer Genome Atlas, genetic mutations have been identified in several genes; KRAS (32.2%), BRAF (7.0%), EGFR 11.3%), ERBB2 (1.7%), ALK fusion (1.3%), MET exon14 (4.3%), RET fusion (0.9%), ROSI fusion (1.7%) and others.

The diagnosis of lung cancer is normally based on CT or PET scans, tissue sampling, sputum or blood testing. Identification of lung cancer in the early stage can be difficult as the symptoms appear to be similar to those of a respiratory infection. If the disease had spread to other parts of the body, it is mostly not curable although the treatment is focused on providing relief from the symptoms and to enable the individual to live longer. According to the Centers for Disease and Prevention, individuals should have an annual lung cancer if they have a history of heavy smoking and are between the ages of 50 and 80 years old.

The lung cancer is typically diagnosed into two types; small cell lung cancer and the most common form, the non-small cell lung cancer.

 Small cell lung cancer (SCLC): This is aggressive cancer accounting for about 10 – 15% of all lung cancers where affected individuals frequently present with an advanced stage of the disease. Although most of the patients respond to first-line chemotherapy, the prognosis remains poor. The two types of SCLC are small cell carcinoma and combined small cell carcinoma.

Non-small cell lung cancer (NSCLC): NSCLC represents around 85% of all lung cancers with an overall 5 year survival rate of 17%, ie., 10-14 months approximately. Over the last decade, important advances have helped with the identification of genetic driver alterations and for the development of novel therapies which has improved the outcomes of these affected individuals. One of the most common subtypes of NSCLC is lung adenocarcinoma which is the abnormal growth of peripheral glandular epithelial tissue.

Drugs used for Hypertension, Angiotensin Converting Enzyme Inhibitors (ACEIs), at Increased Risk of Lung Cancer

Research indicates that one of the effective drugs used for the treatment of hypertension, angiotensin-converting enzyme inhibitors (ACEIs), could be associated with the development of cancer, including lung cancer. Although the use of ACEIs indicates safety for a long term, it results in the accumulation of bradykinin and substance P in the lungs which is reported to contribute to the growth of lung cancer. In a population-based cohort study published in the BMJ, it used the UK Clinical Practice Research Datalink (CPRD) which included data from around 700 general practices comprising of about 15 million patients. This study shows that the use of ACEIs is associated with a 14% increased risk of developing lung cancer and for individuals who continue ACEIs for a longer duration such as 10 years, the risk increases further.


Treatment Advances

  • Tecentriq in Combination with Avastin and Chemotherapy.

A phase 3 trial shows that the addition of Tecentriq to a combination of Avastin and chemotherapy can prolong the survival of patients with non-squamous non-small cell lung cancer. The control group consisted of individuals receiving Tecentriq with carboplatin and Taxol; Tecentriq and Avastin plus carboplatin and Taxol; or Avastin with carcoplatin and Taxol.  The study shows that in comparison to patients receiving Avastin and chemotherapy, those with Tecentriq had prolonged survival (19.2 vs. 14.7 months) and this observation was noted among all the patients including those presenting mutations in the EGFR and ALK genes. Therefore, the study provides significant evidence of survival benefit by adding clinical evidence supporting the use of this combination therapy as the initial treatment for metastatic non-squamous non-small cell lung cancer.

  • BRAF inhibitors for the treatment of non-small cell lung cancer

Drugs were approved for individuals in the treatment of epidermal growth factor receptor (EGFR) mutation or ALK translocation. The EGFR inhibitors and ALK inhibitors have improved the outcomes of patients with NSCLC providing progression-free survival and better toxicity profile indicating that targeting driver mutations can provide better outcomes compared to those receiving standard chemotherapy.  A study was done to show the efficacy of a combination treatment with Dabrafenib plus Trametinib among the NSCLC patients with BRAD V600E mutation. Accordingly, the American Society of Clinical Oncology (ASCO) along with the National Comprehensive Cancer Network (NCCN) recommends testing for BRAF mutation and the combination treatment among individuals with metastatic non-squamous NSCLC.

  • Interventional pulmonology for the diagnosis and treatment of lung cancer

As a growing field in pulmonary medicine, an interventional pulmonologist can be used for the diagnosis and the treatment of lung cancer. With this intervention, the staging of the disease, treatment of central airway obstruction and management of complications occurring as the result of cancer can also be attained. With a current trend in the advances of this technology and procedural technique, the increasing number of pulmonologists also impacts the treatment of lung cancer care.

  • Sodium-Dependent Glucose Transporter 2 (SGLT-2) as Early Diagnostic Marker

A potential marker, the sodium-dependent glucose transporter 2 (SGLT-2), was discovered for the identification of active lung pre-malignancy and early-stage lung adenocarcinomas. The SGLT-2 is identified in the initial tumorigenesis, particularly in the premalignant lesions and well-differentiated adenocarcinomas. The SGLT-2 could be detected by using a combination of immunohistochemistry and with Me4FDG positron emission tomography (PET). Therefore, the targeting of SGLT-2 in lung cancer could prevent the progression of early stages of lung cancer by interrupting the tumor’s supply of glucose.