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Selecting Therapy of Cancer Arising from Respiratory Papillomatosis
In a case of recurrent respiratory papillomatosis with progressive, bilateral tumor
invasion of the lung parenchyma, conditional reprogramming was used to generate
cell cultures from the patient’s normal and tumorous lung tissue. Analysis revealed
that the laryngeal tumor cells contained a wild-type 7.9-kb human papillomavirus
virus type 11 (HPV-11) genome, whereas the pulmonary tumor cells contained a
10.4-kb genome (Yuan et al. 2012 ). The increased size of the latter viral genome
was due to duplication of the promoter and oncogene regions. The spread of the
tumor in the lung was most likely due to the distal aspiration of tumor cells rather
than reinfection of new cells. Finally, the fi nding that the laryngeal tumor lacked the
10.4-kb genome suggests that duplication in the viral genome did not precede exten-
sion into the lung. Chemosensitivity testing identifi ed vorinostat as a potential ther-
apeutic agent, which led to stabilization of tumor size with durable effects. This is a
good example of use of biotechnology to understand the spread of tumor in an
individual patient and selection of appropriate therapy.
Testing for Response to Chemotherapy in Lung Cancer
To gain insight into clinical response to platinum-based chemotherapy (PBC) in
NSCLC, matched tumor and nontumor lung tissues from PBC-treated NSCLC
patients − nonresponders as well as non-responders − and tumor tissue from an inde-
pendent test set were profi led using microarrays (Petty et al. 2006 ). Lysosomal pro-
tease inhibitors SerpinB3 and cystatin C were highly correlated with clinical response
and were further evaluated by immunohistochemistry in PBC-treated patients. This
pathway within tumor cells, not previously suspected to be involved in lung cancer,
was shown to cause resistance to chemotherapy, thus preventing the PBC from kill-
ing the cancer cells. This fi nding has led to the development of a new test that may
allow clinicians to predict whether or not a lung cancer patient will respond to che-
motherapy and help in decision-making about how the patient could best be treated,
therefore, moving lung cancer patients closer to personalized treatments. This fi nd-
ing could also pave the way for the development of new drugs to target this pathway,
which could subsequently lead to more effective treatments for lung cancer.
Polymorphisms in the MDR1 Gene These may have an impact on the expression
and function of P-glycoprotein encoded by it, thereby infl uencing the response to
chemotherapy. Patients harboring the 2677G-3435C haplotype have a statistically
signifi cant better response to chemotherapy compared to those with the other hap-
lotypes combined. Therefore, MDR1 polymorphisms can be used for predicting
treatment response to etoposide-cisplatin chemotherapy in SCLC patients.
NTRK1 Oncogene Fusions A novel class of oncogenes, NTRK1 fusions, were
detected in lung adenocarcinomas by NGS or FISH (Doebele et al. 2013 ). Additional
studies to determine the frequency and characteristics of NTRK1 fusions in lung
cancer are ongoing. These fi ndings suggest that prospective clinical trials of Trk
inhibitors in NTRK1 fusion positive patients may be warranted.
10 Personalized Therapy of Cancer