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The proteins that regulate cell proliferation, metastatic potential, survival in circulation, and immune evasion represent
most of the targets for therapeutic intervention in cancer. Furthermore, genomic profiling of just the cancer cells leaves
critical information about the tumor microenvironment in the dark. The articles highlighted in this Focus Issue describe
efforts to translate genomic data into knowledge of aberrant signaling that can be therapeutically targeted and strat-
egies to explore not only the changes that occur in the protein landscape of the tumors but also in the protein profiles
of the tumor microenvironment.
The Cancer Moonshot initiative aims to bring and multiparametric antigen analysis enable have created protein-level network models to
more effective therapies and diagnostic tools to simultaneous evaluation of tumor heterogeneity predict therapeutic efficacy and resistance mech-
the clinic through increased coordination of and the microenvironment. Simmons et al. anisms in various tumor types. Caromile et al.
Ferrarelli and Gough, Sci. Signal. 10, eaan0430 (2017) 14 March 2017 1 of 3
SCIENCE SIGNALING | EDITORIAL GUIDE
analysis explained a previously puzzling ex- sion of the gene encoding VAV2 and thus L. A Caromile, K. Dortche, M. M. Rahman,
pression profile and uncovered a potential increased abundance and activity of this cyto- C. L. Grant, C. Stoddard, F. A. Ferrer,
therapeutic avenue. Shi et al. looked at protein skeletal regulatory protein that promotes cell L. H. Shapiro, PSMA redirects cell survival
abundance patterns in various cell types and motility and metastasis of the cancer. Thus, signaling from the MAPK to the
found that the abundance of adaptor proteins knowing whether a gene contains mutations PI3K-AKT pathways to promote the
not the receptoris rate-limiting in dictating or exhibits altered expression is only the be- progression of prostate cancer. Sci. Signal.
the signaling intensity and biological output ginning of unraveling the molecular details re- 10, eaag3326 (2017). [Abstract]
of the epidermal growth factor receptor (EGFR) quired to understand a tumor and develop and
pathway. This suggests that targeting adaptors apply effective treatment strategies. Research- D. R. Croucher, M. Iconomou,
rather than the receptor may be more effective ers must examine the function, modification, J. F. Hastings, S. P. Kennedy,
at suppressing growth-promoting signals in localization, and interaction networks of the J. Z. R. Han, R. F. Shearer, J. McKenna,
tumor cells. Croucher et al. applied a method encoded proteins in tumor cells and cells of A. Wan, J. Lau, S. Aparicio,
that detected dimer-specific conformations of the tumor microenvironment. The articles high- D. N. Saunders, Bimolecular
proteins to breast cancer cells. They found that lighted here exemplify just some of the cancer complementation affinity purification
distinct dimer formation between members of research published in Science Signaling, and, like (BiCAP) reveals dimer-specific protein
the EGFR family is associated with distinct in- some of the Cancer Moonshot initiatives, these interactions for ERBB2 dimers.
teraction networks of adaptors and other pro- studies reveal basic aspects of cancer biology Sci. Signal. 9, ra69 (2016). [Abstract]
teins and consequently produces different that can be leveraged for patient stratification
C. Gamell, T. Gulati, Y. Levav-Cohen,
Ferrarelli and Gough, Sci. Signal. 10, eaan0430 (2017) 14 March 2017 2 of 3
SCIENCE SIGNALING | EDITORIAL GUIDE
C. Ruggiero, M. Doghman-Bouguerra, cancer. Sci. Signal. 10, eaah4674 (2017). coordination between signaling pathways
S. Sbiera, I. Sbiera, M. Parsons, [Abstract] is revealed in human colorectal
B. Ragazzon, A. Morin, E. Robidel, cancer using single-cell mass
J. Favier, J. Bertherat, M. Fassnacht, Research Resources cytometry of archival tissue blocks.
E. Lalli, Dosage-dependent regulation of T. Shi, M. Niepel, J. E. McDermott, Sci. Signal. 9, rs11 (2016). [Abstract]
VAV2 expression by steroidogenic Y. Gao, C. D. Nicora, W. B. Chrisler,
factor-1 drives adrenocortical carcinoma G. Zhang, H. Scarborough, J. Kim,
L. M. Markillie, V. A. Petyuk,
cell invasion. Sci. Signal. 10, eaal2464 A. I. Rozhok, Y. A. Chen, X. Zhang,
R. D. Smith, K. D. Rodland, P. K. Sorger,
(2017). [Abstract] L. Song, Y. Bai, B. Fang, R. Z. Liu,
W.-J. Qian, H. S. Wiley, Conservation
J. Koomen, A. C. Tan, J. Degregori,
of protein abundance patterns reveals
C. Thomas, W. Henry, B. G. Cuiffo, the regulatory architecture of the
E. B. Haura, Coupling an EML4-ALK
A. Y. Collmann, E. Marangoni, centric interactome with RNA interference
EGFR-MAPK pathway. Sci. Signal. 9,
V. Benhamo, M. K. Bhasin, C. Fan, identifies sensitizers to ALK inhibitors.
rs6 (2016). [Abstract]
L. Fuhrmann, A. S. Baldwin, C. Perou, Sci. Signal. 9, rs12 (2016). [Abstract]
A. Vincent-Salomon, A. Toker, A. J. Simmons, C. R. Scurrah, 10.1126/scisignal.aan0430
A. E. Karnoub, Pentraxin-3 is a E. T. McKinley, C. A. Herring, Citation: L. K. Ferrarelli, N. R. Gough, Focus Issue: Cancer
PI3K signaling target that promotes J. M. Irish, M. K. Washington, Beyond tumor genetics to protein landscapes. Sci. Signal. 10,
stem celllike traits in basal-like breast R. J. Coffey, K. S. Lau, Impaired eaan0430 (2017).
Ferrarelli and Gough, Sci. Signal. 10, eaan0430 (2017) 14 March 2017 3 of 3
Focus Issue: CancerBeyond tumor genetics to protein
landscapes
Leslie K. Ferrarelli and Nancy R. Gough (March 14, 2017)
Science Signaling 10 (470), . [doi: 10.1126/scisignal.aan0430]
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