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individual protein signals in the molecular weight range from 2,000 to over 200.
LCM, in combination with MS, enables acquisition of protein signatures from a
single cell type within a heterogeneous sample. These signals directly correlate with
protein distribution within a specifi c region of the tissue sample. The systematic
investigation of the section allows the construction of ion density maps, or specifi c
molecular images, for virtually every signal detected in the analysis.
MALDI TOF MS can be used to generate protein spectra directly from frozen
tissue sections from surgically resected cancer specimens. Profi ling MALDI MS
has been used to monitor alterations in protein expression associated with tumor
progression and metastases. Current data suggests that MALDI MS will be superior
to immunohistochemical stains and electron microscopy in identifying the site of
origin for tumors currently labeled as “tumor of unknown primary”. Another appli-
cation in surgical pathology would be the rapid evaluation of margins of surgical
excision of a tumor. Routine analysis of surgical margins by frozen section is very
diffi cult because some cancers invade in a single cell fashion without producing a
grossly identifi able mass. Sensitivity of MS enables detection of even a few tumor
cells within a signifi cantly larger portion of tissue.
The capability of MALDI MS to measure susceptibility and response to thera-
peutic agents in tumor and surrounding tissues is particularly useful in personalized
management of cancer. The original protein profi le obtained from the primary tumor
can be used to infl uence the selection of therapeutic agents. Levels of chemothera-
peutic agents can be measured directly from a tissue biopsy to assess adequacy of
delivery to a particular organ site. It will also help in detecting alterations in specifi c
molecular pathways directly modulated or indirectly affected by the anticancer
agent. Finally, it could be used to monitor chemotherapy effects on the tumor.
Role of Sequencing in Personalized Therapy of Cancer
Discoveries made through application of the human genome sequencing have
already an impact on practice of oncology and have infl uenced the design of clinical
trials for new cancer therapies. Sequencing the entire TP53 gene from various types
of cancer using next-generation sequencing (NGS) with ultradeep coverage has
enabled a curated mutation database for TP53 mutations and a framework for muta-
tion database analysis (Edlund et al. 2012 ). Such databases are expected to play
central roles in personalized medicine by providing targets for drug development
and biomarkers to tailor treatments to each patient.
Comprehensive analysis of the genome sequence of individual cancers has
helped uncover the specifi c mutations that contribute to the malignant phenotype,
identify new targets for therapy, and increase the opportunities for choosing the
optimal treatment for each patient, e.g. lung adenocarcinoma can now be divided
into subtypes with unique genomic fi ngerprints associated with different outcomes
and different responses to particular therapies (Collins and Hamburg 2013 ). Findings
from the Cancer Genome Atlas demonstrate that the tissue of origin of a particular
10 Personalized Therapy of Cancer