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Clinical Stem 1
Non-smoking female with a new right upper lobe lung mass and three PET-positive mediastinal lymph nodes

Answer D
While data regarding clinical use is still emerging, all markers listed above could impact management. Testing for these markers is relevant if clinical trials are accessible to the patient. ERCC1, RRM1 and TS could predict response and or resistance to certain chemotherapy agents. ERCC1 is an important component of nucleoside excision repair. Because platinum-based chemotherapy works by creating platinum-DNA adducts, increased levels of ERCC1 indicate resistance to platinum-based therapy while low levels indicate sensitivity. The regulatory sub-unit of ribonucleotide reductase, also known as RRM1, is the target of gemcitabine. In some studies, high levels of RMM1 are associated with gemcitabine resistance and poor outcome. High levels of TS indicate pemetrexed resistance, but levels are usually higher in squamous cell compared with adenocarcinoma histology, which may be why squamous cell carcinoma does not respond to pemetrexed.

In patients treated with TK inhibitors for EGFR positive lung cancer, adaptive resistance commonly develops during therapy. Mechanisms of resistance include T790M mutation and MET amplification. If tested positive, this patient could be enrolled in clinical trials directed towards these molecular markers.
References:
  1. Olaussen et al: DNA Repair by ERCC1 in Non?Small-Cell Lung Cancer and Cisplatin-Based Adjuvant Chemotherapy. N Engl J Med. 2006;355:983-991.
  2. Rosell R et al: Ribonucleotide reductase mRNA expression and survival in gemcitabine/cisplatin-treated advanced non-small-cell lung cancer patients. Clin Cancer Res 10:1318-1325, 2004.
  3. Kobayashi S et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005;352(8):786.
  4. Cipriani NA et al. MET as a target for treatment of chest tumors. Lung Cancer. 2009;63(2):169.
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