Identification of biomarkers for the detection of small cell lung cancer

2013

Early Detection Research Award

Ignacio I. Wistuba, MD

University of Texas MD Anderson Cancer Center

Houston

Humam Kadara, PhD

University of Texas MD Anderson Cancer Center

Houston

Dr. Wistuba and his colleague Dr. Humam Kadara are identifying biomarkers that could ultimately lead to the fist test to detect small cell lung cancer in its earliest and most treatable stages.

Research Summary

There is a lack of strategies for detection of small cell lung cancer (SCLC), a difficult-to-treat lung cancer subtype, which we believe is due to our poor understanding of the molecular development of the disease. Moreover, while screening by clinical measures reduces lung cancer mortality, the detected lung cancers are less likely to be SCLCs warranting the need for additional detection methods (e.g., biological).

Our earlier work revealed cancer-associated markers and profiles in “normal” (to the “eye”) airways close to lung tumors, an effect we refer to as “molecular field cancerization,” in which there is field around the tumor that is enriched with malignant properties. We found field effects in “normal” airways that increased with time following tumor removal were different between patients with and without lung cancer or different subtypes of the disease, and were present in other respiratory tract compartments, including the nose.

Although we previously found that airways near SCLCs display excessive genetic abnormalities, the molecular field effect in SCLC and its relevance to detection of the disease is unknown. The proposed project aims to characterize, by high-throughput technologies, the molecular makeup of cells lining the nose and airways and of tumors from the SCLC patients compared to molecular profiles of samples from patients with benign disease or other lung cancer types, and then test these markers for their capacity to detect SCLC in easily accessible sites. We expect by using such unique resources and approaches to delineate novel markers for SCLC detection.

Technical Abstract

Small cell lung cancer (SCLC) exhibits aggressive clinical behavior and poor outcome and response to therapy. Moreover, there are no effective strategies for early detection of SCLC. Therefore, there is an urgent need to identify new strategies and markers for SCLC detection. We recently characterized the molecular airway field cancerization (FC) in non-small cell lung carcinoma (NSCLC) patients and identified airway profiles that varied spatially (n=1165) and with time (n=1395) following surgery. Moreover, we characterized the adjacent airway FC in NSCLC (n=1606 genes), a subset of which (n=299) significantly distinguished airways of smokers with lung cancer from those of healthy smokers and another (n=208) separated airways of different NSCLC subtypes. Although we previously showed that SCLCs and adjacent airways are characterized by higher level of allelic losses compared to those of NSCLC cases, the global airway FC in SCLC and its relevance to detection has not been explored. We hypothesize that the molecular airway FC in SCLC is different compared to that in NSCLC or benign lung disease and comprises biomarkers specific for early detection of SCLC. We will 1) perform global expression profiling of the airway FC and tumors or nodules in patients with SCLC, NSCLC, and benign disease for identification of airway markers specific to SCLC and 2) test identified airway mRNA markers for SCLC detection in bronchial and nasal compartments in patients with suspect lung cancer. We anticipate that our proposal, due to its unique resources and approaches, will identify novel markers for SCLC detection.

Key words

Adenocarcinoma

Biomarker or biomarker testing

Early detection

Molecular profile or molecular testing

Non-small cell lung cancer (NSCLC)

Risk profile

Screening

Small cell lung cancer (SCLC)

Squamous cell lung cancer

Identification of biomarkers for the detection of small cell lung cancer

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