DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Validation of microRNA and Inflammatory Gene Biomarkers that Predict Prognosis and Therapeutic Outcome in Lung and Colon Adenocarcinoma

Principal Investigator: HARRIS, CURTIS C
Institution Receiving Award: THE GENEVA FOUNDATION
Program: PRMRP
Proposal Number: PR093793
Award Number: W81XWH-10-2-0031
Funding Mechanism: Investigator-Initiated Research Award
Partnering Awards:
Award Amount: $673,115.00


PUBLIC ABSTRACT

Both lung and colon cancer are deadly diseases that kill over 200,000 people annually in the United States. Discovering new prognostic biomarkers for these diseases has the potential to change the standard of care and may improve survival outcomes for some patients. Biomarkers that predict poor therapeutic outcome may predict the need for alternative or more aggressive therapeutic intervention at earlier times than compared to the current practice. Additionally, in cancer patients that have no detectable metastases, prognostic biomarkers may suggest the presence of micro-metastases, indicating a patient should receive adjuvant therapy rather than surgery alone.

We have previously performed molecular profiling of tumors to identify inflammatory gene and microRNA expression patterns that predict poor survival for both lung and colon cancer. In these studies we found that we could predict poor survival prognosis for stage I lung cancer and stage II colon cancer. Biomarkers predicting poor survival in stage I lung cancer suggest undetectable micro-metastases are present and surgery alone will not be curative. It is controversial if stage I lung cancer patients should be treated with adjuvant therapy. Our findings indicate that the inflammatory gene and microRNA biomarkers have the potential of guiding therapeutic decisions for these patients. The result could be providing therapy to high-risk stage I cancer patients with likely micro-metastases while avoiding the unnecessary treatment to those stage I patients where surgery is curative. Similarly, biomarkers predicting poor survival in stage II colon cancer patients would suggest that micro-metastases are present and surgery will not be curative. It is also controversial if stage II colon cancer patients should be treated with adjuvant therapy since surgery for many patients will be curative. Our findings indicate that inflammatory gene and microRNA expression patterns can predict poor survival in stage II patients and may aid in deciding which stage II patients should receive therapeutic intervention.

For our studies in colon and lung cancer, we have used multiple cohorts to find and validate these biomarkers. This strategy gives us confidence that these biomarkers are representative of the majority of cancers. Nevertheless, further validation of these biomarkers is a crucial step required prior to committing resources for expensive prospective studies and clinical trials using these biomarkers. We propose to conduct validation studies of these biomarkers and indentify new biomarkers using molecular profiling techniques. If this study validates our previous findings, it will bring the inflammatory gene and microRNA biomarkers one step closer to clinical use.