Textbook of Personalized Medicine - Second Edition [2015]

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prognosis group (cathepsin D, ENO1, and VDAC1) to confi rm that the proteins
indeed originated from the tumor and not from a stromal or infl ammatory compo-
nent. Overall, these fi ndings show how in-depth analysis of clinical material can
lead to an increased understanding of the molecular mechanisms underlying tumor
progression. This study shows a functional coupling between high glycolytic activ-
ity and postsurgical relapse of adenocarcinoma of the lung. Protein level changes
detected in this study could serve as starting point for discovery of predictive bio-
markers for metabolic treatment options in lung cancer.


Role of microRNAs as Biomarkers of Lung Cancer


Alterations in expression profi les of microRNAs (miRNAs) are linked to lung can-
cer. Serum miR-148a, miR-148b, and miR-152 are signifi cantly downregulated in
NSCLC patients, whereas there is overexpression of serum miR-21 (Yang et al.
2014 ). The combination of these four candidate miRNAs exhibits higher predictive
accuracy in NSCLC screening compared with individual miRNAs. Rule discovery
followed by distance separation is a powerful computational method to identify reli-
able miRNA biomarkers (Song et al. 2014 ). For example, if the expression level of
miR-98 is >7.356 and the expression level of miR-205 is <9.601, the sample is
normal rather than cancerous with specifi city and sensitivity both 100 %.
miRNAs have been shown to control the expression of cognate target genes and
predict relapse in surgically resected NSCLC patients. Overexpression of the
Wingless-type (Wnt) genes and methylation of Wnt antagonists have been docu-
mented in NSCLC. Understanding the relevance of these fi ndings can help to change
the clinical practice in oncology towards customizing chemotherapy and targeted
therapies, leading to improvement in both survival and in cost-effectiveness.


Role of a New Classifi cation System in the Management of Lung Cancer


Apart from genotyping, a new staging system that was developed by the International
Association for the Study of Lung Cancer will have a considerable impact on the
future management of lung cancer. Changes in the new classifi cation include: creat-
ing more sub-stages for tumor size, reassigning some large tumors to a more
advanced stage, reclassifying tumors that have spread into the fl uid surrounding the
lung, and recognizing that spread to certain lymph nodes is more dangerous than its
spread to others. By changing these groupings, some patients will get moved to an
earlier stage of disease that may be treated more aggressively. For example, a
patient may have only been offered chemotherapy but may now be offered chemo-
therapy and radiation or more intense radiation. Conversely, some people consid-
ered to have earlier-stage tumors now will be grouped with those whose tumors
have widely spread and discouraged from undergoing therapies that have little
chance of helping them.


Personalized Management of Cancers of Various Organs

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