Contemporary lung cancer therapy requires an understanding of the molecular composition and biologic activity of individual tumor cells. Advances in laboratory technique, characterization of biomarkers and the identification of genetic alterations have facilitated a transformation in the diagnosis and management of patients with lung cancer in 2015. Therefore, a lung tumor diagnosed today requires both accurate pathologic subtyping and genomic analysis to determine the optimal therapy.
Genomic testing of lung tumors has become a new standard of care now that genetic factors have been identified in the development of virtually all cancers. Lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are among the best understood. Consequently, “small molecule” therapy targeting the respective oncogenic pathways related to these target molecules have been developed and continue to be investigated.
Erlotinib and crizotinib respectively, are examples of such medications that are classified as tyrosine kinase inhibitors (TKIs). By targeting these specific molecules, investigators aim to preferentially kill malignant cells while preserving normal tissues. From a patient’s perspective, the enhanced sensitivity toward tumor cells translates to fewer side effects and improved survival when compared to more traditional systemic chemotherapy.
However, despite the recent progress of targeted therapies, these medications are not curative, and disease relapse consistently occurs through acquired resistance. Another major barrier to the advancement of lung cancer therapy includes the high level of heterogeneity inherent to lung cancer genomics. Whereas a handful of identifiable markers are associated with a majority of breast cancers, our current understanding of lung cancer encompasses only about 20 percent of such tumors.
The variety of oncogenic alterations present in lung cancer appears to be far more numerous, and therefore much work remains. Many more new molecular targets will need to be identified, and ultimately clinical trials will need to be performed. Northside Hospital (NSH) seeks to become a leader in lung cancer related research through an array of public and private partnerships.
In association with the Addario Lung Cancer Medical Institute (ALCMI) in San Carlo, Calif., and its sister organization, The Bonnie J. Addario Lung Cancer Foundation (BJALCF), patients may participate in studies aimed to identify new molecular targets and advance our understanding of lung cancer genomics. In a collaborative manner, ALCMI aims to identify unique populations of lung cancer patients with unique molecular targets by collecting proteomic, genomic, molecular and clinical data across a multitude of institutions and oncology networks. The ultimate goal is development of more novel and targeted therapies to further impact the lives of lung cancer patients.
The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is another important study open for patient enrollment at NSH. This study is sponsored by the National Cancer Institute (NCI) and similarly seeks to analyze tumor specimens and identify genetic targets. In addition, ALCHEMIST investigators will study the efficacy of genetic-based drugs among surgically resected patients with EGFR or ALK positive lung cancer in reducing recurrence among patients at earlier stages of disease.
Patients with squamous cell carcinoma (SCCA) of the lung demonstrate a genetically distinct morphology when compared to adenocarcinoma and its related mutations described above. Furthermore, delineation of molecular genotyping and the development of appropriate targeted therapy aimed at SCCA has lagged. Subsequently, the NCI,NSH and the cancer research cooperative group SWOG Cancer Research, among others, are collaborating to enroll patients in the Lung-MAP clinical trial.
The Lung-MAP clinical trial will test the efficacy of five investigational drugs. The study aims to build on the demonstrated progress against adenocarcinomas of the lung by matching treatment regimens against specific mutations found among patients with SCCA. Patients with SCCA who have failed first-line conventional therapies are eligible for enrollment.
