New molecularly targeted therapies for lung cancer

Abstract

Global cancer statistics indicate that lung cancer is responsible for over 1 million deaths each year (1). Approximately 80%-85% of all lung cancers are non-small cell lung cancer (NSCLC), which include squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Small cell lung cancer (SCLC) represents approximately 15%-20% of cases, and the incidence of SCLC has been decreasing over the last several years in the United States (2). Current treatment options include surgical resection, platinum-based doublet chemotherapy (a combination of two drugs that includes carboplatin or cisplatin as the backbone), and radiation therapy alone or in combination. Unfortunately, despite these therapies, the disease is rarely curable and prognosis is poor, with an overall 5-year survival rate of only 15% (3). This article will review recent advances and future perspectives in the development of novel strategies for the treatment of lung cancer, with an emphasis on how these can be derived from our understanding of the molecular pathogenesis of the disease. Historical perspectiveIn the mid-1800s, lung cancer was a rare disease, representing only 1% of all cancers seen at autopsy. By the early 1900s, the incidence of malignant lung tumors had begun to rise, and although most lung cancers occurred in men, a steady increase in women was observed beginning in the 1960s. While the link between cigarette smoking and lung cancer was suspected by clinicians in the 1930s, the cause of the dramatic increase was not well established until landmark epidemiologic studies in the 1950s provided evidence for a strong causal association between smoking and lung cancer (4). Surgical therapy for lung cancer began in the 1930s, with the first successful pneumonectomy for lung cancer reported by Evarts Graham in 1933 (5). The prognostic significance of nodal metastases was subsequently recognized, and surgical mediastinal lymph node sampling became an important aspect of staging. Current surgical approaches use lobectomy or, if necessary, pneumonectomy for curative treatment, while wedge resections are reserved for patients with severely impaired lung function. Likewise, preoperative evaluation and postoperative care have improved, resulting in operative mortality rates of less than 5%. With the invention of megavoltage linear accelerators, radical radiotherapy for potential cure of lung cancer was introduced in the 1950s. There have been significant technologic developments in radiation therapy planning and delivery such that currently, approximately 15% of patients with early-stage disease can be cured with radiotherapy alone. Nitrogen mustard was the first chemotherapy used for the treatment of lung cancer in the 1940s. Pilot studies from the late 1970s and early 1980s identified other drugs with activity against lung cancer, particularly drug combinations using cisplatin with a vinca alkaloid or etoposide (6). Over the next two decades, several prospective, randomized studies were conducted to evaluate various chemotherapy regimens (6, 7)...

Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer

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TAZ is a novel oncogene in non-small cell lung cancer

“…Despite the advancement in surgical, radio-and chemo-therapies over the years, the 5-year survival rate of lung cancer remains o15% (Sun et al, 2007), underscoring the aggressive nature of this disease. Of lung cancers diagnosed, over 80% are non-small cell lung cancer (NSCLC), which includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma (Yokota and Kohno, 2004).…”

Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines

“…In addition, mutations and amplifications of the epidermal growth factor receptor are also very common in NSCLC (Linardou et al, 2009). These mutations provide the basis for the development of targeted therapies for this subtype of cancer (Sun et al, 2007). Although improved therapy is available, the median survival of late-stage disease is less than 1 year.…”