Biomarkers for personalizing adjuvant therapy in NSCLC – increasing cures

2011

Therapeutics Award

David P. Carbone, MD, PhD

The Ohio State University

Columbus

John Minna, MD

University of Texas Southwestern Medical Center

Dallas

Ignacio Wistuba, MD

University of Texas MD Anderson Cancer Center

Houston

Patients with stage I and II lung cancer usually undergo surgery to treat their cancer. Sometimes, the cancer comes back. Using chemotherapy with surgery can prevent the cancer’s return. Dr. Carbone is studying how we can identify which stage I and II patients may benefit from chemotherapy.

Research Summary

Even with all of the targeted therapies being developed today, lung cancer is only curable when diagnosed early enough for surgical resection, or combined chemotherapy and thoracic radiation. The recent finding that screening CTs to identify early stage lung cancers can reduce mortality also refocuses our efforts on improving the definitive therapy of localized disease. In most studies, however, cure rates for stage I or II lung cancers are between 50 and 70%, and chemotherapy after surgery improves this only a few percent, and chemotherapy is toxic in almost all patients. The point of these studies is to increase the number of cures achieved in patients with early stage lung cancer and minimize the side-effects of therapy by attacking 3 goals: 1) identifying which tumors are likely to relapse and thus might benefit from additional therapy, 2) identifying which patients will benefit from the addition of chemotherapy after surgery, and 3) figuring out which signals in tumors are associated with those that will relapse to define new types of treatment targeted at these signals. We will take the novel approach of using both state-of-the-art evaluation of both proteins and genes in the same cells to define these groups.

Technical Abstract

The most effective curative modality we have for lung cancer is still surgery, but, even with optimum surgery, many patients relapse and die of their lung cancer, and this fraction is improved only slightly by adjuvant chemotherapy, which is nonetheless toxic for everybody. Thus, we need to identify prognostic biomarkers (to define which patients are likely to relapse after surgery) and predictive biomarkers (to define who will benefit from adjuvant therapy, and what specific type of adjuvant therapy should be used on each particular patient). In this proposal, collaborators from two different lung cancer SPOREs in three different universities will use two sets of high information-content analyses of protein and RNA expression already acquired on a cohort of early-stage lung cancer patients who did not receive adjuvant chemotherapy and in a panel of cell lines rigorously characterized for sensitivity to platinum doublets, and will add to that data funded by this proposal on a new cohort of patients treated with adjuvant chemotherapy to generate our classifier. This classifier will then be reduced to a small number of RNA or protein assays and tested in a larger set of resected patients with and without adjuvant chemotherapy.

Key words

Adenocarcinoma

Biomarker or biomarker testing

Chemotherapy

Molecular profile or molecular testing

Non-small cell lung cancer (NSCLC)

Biomarkers for personalizing adjuvant therapy in NSCLC – increasing cures

LUNGevity Foundation

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