Circulating Tumor Cells (CTCs) as a Blood-based Tumor Marker in Patients With Small Cell Lung Cancer (SCLC)

Small cell lung cancer (SCLC) is characterized by early dissemination through the blood
system with the majority of patients succumbing to their disease in 9-11 months. Despite
evaluation of multiple new agents a platinum doublet has remained the standard of care for
over 25 years. We believe that the lack of understanding of the biology of SCLC has
contributed to our failure to advance treatment and prolong survival. Tumor and blood
biomarkers have been shown to be a powerful tool for increasing our understanding of the
complex biology of cancer and determining prognosis and response to therapies. Currently,
there are no validated biomarkers for response or to follow disease activity in SCLC.
Detection of Circulating Tumor Cells (CTCs) is a laboratory technique that became available
in the last few decades. Newer, more sensitive technology for the isolation and
characterization of CTCs using a rare event imaging system with automated fluorescence
microscopy known as CellSearch has demonstrated value in several cancers. CTCs detection by
this system is approved as a prognostic biomarker in metastatic breast cancer, and as a tool
to monitor disease in metastatic colorectal cancer and castrate resistant prostate cancer.

To date, only one publication has reported on the presence of CTCs in SCLC. These
investigators used RT-PCR to amplify CK19 cDNA. CTCs were detected in 27% of patients. In
our preliminary study using the CellSearch system we have detected 1 or more CTCs in 11/13
(84%) patient samples in various stages of their disease. Thus CTCs may be a promising
biomarker but we need more studies. Thus, our first goal is to determine if CTCs in SCLC
can predict response to chemotherapy, predict early relapse or function as a as a prognostic
marker.

In addition, we will explore the feasibility of extracting genetic material from CTCs for
genomic profile that could immensely help us unravel the complex molecular pathways and gene
expression in SCLC, which ultimately will lead to novel drug development. Other
investigators have shown that gene expression profiles for CTCs may be used to distinguish
normal donor from advanced cancer patients and differentiate among different types of
cancers.

In summary, SCLC kills 45,000 Americans each year. The treatment of SCLC has not changed
since the introduction of cisplatin and etoposide during 1970s. Research in cancer biology
has identified several genetic alterations that could be of therapeutic importance. Novel
agents that target these genetic alterations are currently in development. Patient selection
will be key in order to determine the activity of these agents. Understanding the biology of
this disease is the key to successful interventions and personalizing therapy.

Inclusion Criteria:

- Histological proof of small cell lung cancer with extensive stage disease and have
been untreated.

- Must be willing to give and sign informed consent.

- Must be 18 years of age

Exclusion Criteria:

- Less than 18 years of age.