Improvement in Lung Cancer Outcomes With Targeted Therapies: An Update for Family Physicians

Abstract

In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. The past decade has witnessed a silent revolution in the war against cancer, thanks to the advent of new therapies, which target specific mutations related to cancer cell proliferation and survival in different types of tumors. Among all cancers, lung cancer remains the leading cause of cancer-related death in most countries, with 159,260 expected deaths in the United States in 2014. Lung cancer occurs predominately in people between 50 and 70 years old, but the risk of developing this cancer reaches a peak in people older than 70 years. Lung cancer incidence decreased in the past two decades in several countries, including the United States, following a decreased rate of smoking. At the same time, the incidence among women, including former or never smokers, is rapidly increasing.1 The discovery of "oncogenic driver mutations" and the subsequent development of tailored agents has radically changed the treatment of lung cancer in ten years, leading to the development of personalized strategies. 2,3 Non-small-cell lung cancer (NSCLC) was traditionally classified, based on histologic features, as adenocarcinoma, squamous cell carcinoma, and other nonspecified subtypes, which represent about 55%, 35%, and 10% of all NSCLC cases, respectively. In the early 1990s treatment approaches available for patients with lung cancer were poor, with a median survival of 2 to 4This article was externally peer reviewed.

Quantitative Secretomic Analysis Identifies Extracellular Protein Factors That Modulate the Metastatic Phenotype of Non-Small Cell Lung Cancer

“…Cancers of the lung and bronchus are a set of devastating diseases, which kill 159,260 Americans in 2014(1). Based on etiological and pathological differences, lung cancer can be divided into two major histotypes, namely non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC)(2).…”

Practical, Office-based Interventions That Improve Care Today

“…Rolfo et al 10 provide an excellent update on the changing fate of lung cancer, and the world of genetics is the reason. Some lung cancers can now be identified by mutations and treated with specific medications.…”

Withaferin a synergistically enhances the effects of paclitaxel against lung cancer.

“…To overcome the challenges with cytotoxic compounds like PAC, targeted therapies and immune checkpoint inhibitors have been developed and approved for NSCLC treatment. However, even with these drugs, it is widely reported that only 60% of NSCLC tumors show targetable mutations and only 25% of patients benefit from immunotherapy [25]. Therefore, there is an unmet need to develop safe and efficacious drugs for the treatment of advanced lung cancer.…”

“…This led to the discovery of molecular mutations that drive the progression of cancers and subsequently the introduction of targeted therapies into clinical practice [14,25]. These targeted therapies interact with specific molecular drivers involved in carcinogenesis, cell proliferation, apoptosis, and metastasis of cancer cells.…”

“…Several reports indicate that the most promising agents for lung cancer are those agents targeting receptor tyrosine kinases (RTKs), mitogen-activated protein kinases (MAPKs) and Janus kinase (JNK) pathways [4,14,17]. Indeed, agents targeting EGFR mutations (erlotinib and gefitinib), ALK gene rearrangements (crizotinib and ceritinib), HER2 mutations (trastuzumab) and angiogenesis (bevacizumab) are currently approved as targeted therapies for NSCLC [17,25,26]. Furthermore, the anti-EGFR agent erlotinib is also approved by FDA as second-line agents for relapsed lung cancer.…”