and is also used for profiling of kinases in other cancer tissues.^23 Despite the
heterogeneity of tumor tissue,^24 Pieborn et al.^25 recommend this method for
determination of phosphoprotein-driven molecular changes after treatment with a
combination of synthetic kinase inhibitors and monoclonal antibodies as valuable
information for physicians to be used for personalized cancer treatment, in this case
the efficacy of the treatment of metastatic colorectal cancer with the protein kinase
inhibitor Imatinib, and Panitumumab, a monoclonal antibody against cell surface
protein epidermal growth factor receptor (EGFR).
Monoclonal antibodies, e.g. against cell surface proteins that are involved in the
activation of signaling network, are now frequently used for efficient cancer
therapy. In order to enhance their efficiency and minimize resistance, these anti-
bodies are combined with synthetic inhibitors. Because of intratumor heterogene-
ity,^26 the rational combinatorial drug design is the method of choice in personalized
cancer medicine strategy.^27 Laser capture microdissection of frozen or formalin-
fixed and pararaffin-embedded (FFPE) biopsies, coupled with RPPA, has been used
for the evaluation of changes of the kinases in primary human colorectal carcino-
mas and mapping of progression of metastases^28 in profiling metastases of prostate
cancer;^29 glioblastoma;^30 pancreatic,^31 rectal,^32 and ovarian cancer,^33 as well as
Ewing sarcoma family of tumors and desmoplastic small-round-cell tumors.^34
RPPA is also preferably used for the measurement of total and phosphorylated
HER2 in the context of HER2 family signaling in human breast cancer.^35 Few
applications listed above stress the necessity of the development of antibodies for
profiling the human proteome and use of the Human Protein Atlas as resource not
only for personalized cancer research^36 but also for the investigation of other
diseases.^37 The Human Protein Atlas project was initiated in 2003 to pursue a
systematic, high-throughput generation of affinity purified polyclonal antibodies.
Subsequent immunohistochemistry- and immunofluorescence-based profiling of
protein expression patterns in tissue and cells is used to generate an expression
(^23) Grubb et al. ( 2009 ), pp. 3044–3054.
(^24) Gerlinger et al. ( 2012 ), pp. 883–892.
(^25) Pieborn et al. ( 2014 ), pp. 2846–2855.
(^26) Al-Lazikani et al. ( 2012 ), pp. 679–691.
(^27) Al-Lazikani et al. ( 2012 ), pp. 679–691.
(^28) Grubb et al. ( 2009 ), pp. 3044–3054.
(^29) Gerlinger et al. ( 2012 ), pp. 883–892; Drake et al. ( 2013 ), pp. E4762–E4769.
(^30) Mueller et al. ( 2014 ), pp. 818–828.
(^31) Campbell et al. ( 2010 ), pp. 1109–1113.
(^32) Erben et al. ( 2008 ), pp. 1544–1550.
(^33) Alberts et al. ( 2007 ), pp. 784–788.
(^34) Chao et al. ( 2010 ), pp. 547–552.
(^35) Wolfkuhle et al. ( 2012 ), pp. 6426–6435.
(^36) Masuda and Yamada ( 2014 ), pp. 651–657.
(^37) Asplund et al. ( 2012 ), pp. 2067–2077; Ponten et al. ( 2011 ), pp. 428–446.
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