Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States.
About 90% of CRC related deaths are due to metastatic spread—mostly to the liver and lungs.
With adequate multidisciplinary patient selection, CRC liver and lung metastasectomy
significantly improves survival and offers the best chance for a cure. However, patients with
limited lung or liver metastases are clinically underserved and poorly scientifically
studied. The individual indication for resection and the decision making for adjuvant
systemic therapies remains a challenge. More sensitive techniques to detect occult disease
are needed for metastatic CRC (mCRC) patients, and perioperative analysis of circulating
tumor cells (CTCs) may provide an outstanding opportunity to develop such innovative methods.
We hypothesize that CTCs are enriched during CRC liver and/or lung metastasectomy, and that
they can be isolated and characterized in an attempt to identify novel therapeutic targets.
CTCs are believed to be causing metastasis and may provide a non-invasive alternative to
organ biopsies for the detection, characterization and monitoring of solid cancers. CTC
numbers have been shown to be a strong predictor of Progression Free Survival and Overall
Survival for mCRC patients. The CellSearch system (Veridex LLC, Ratinas, NJ, USA) currently
is the only FDA approved test for the evaluation of CTC numbers in metastatic breast,
prostate and colorectal cancer. However, the rarity of CTCs in the blood leads to limited
capture efficiency and the CellSearch system fixes cells, preventing further molecular
characterization of CTCs by functional assays and primary cell culture. In this protocol the
CellSearch system will be compared to a new technology, called the Flexible Micro Spring
Array (FMSA) device, developed by Dr. Zheng, Department of Bioengineering, Penn State
University, University Park. This novel approach enables size-exclusion based filtration for
viable CTC enrichment. The FMSA device is inexpensive, works rapidly, and retains viable CTCs
for further biological study. Using both the CellSearch system and the FMSA device, we will
determine the kinetics of CTC shedding into circulation, develop an effective system for
isolation, enumeration, and further enrichment CTCs, and use this system to find
characteristics of different CTC populations.