A colorectal cancer classification system that associates cellular phenotype and responses to therapy

@article{Sadanandam2013ACC,
  title={A colorectal cancer classification system that associates cellular phenotype and responses to therapy},
  author={Anguraj Sadanandam and Costas Andreas Lyssiotis and Krisztian Homicsko and Eric A. Collisson and William J. Gibb and Stephan Wullschleger and L. Ostos and William A. Lannon and Carsten Grotzinger and Maguy del Rio and Beno{\^i}t Lhermitte and Adam B. Olshen and Bertram Wiedenmann and Lewis C. Cantley and Joe W. Gray and Douglas Hanahan},
  journal={Nature Medicine},
  year={2013},
  volume={19},
  pages={619-625}
}
Colorectal cancer (CRC) is a major cause of cancer mortality. Whereas some patients respond well to therapy, others do not, and thus more precise, individualized treatment strategies are needed. To that end, we analyzed gene expression profiles from 1,290 CRC tumors using consensus-based unsupervised clustering. The resultant clusters were then associated with therapeutic response data to the epidermal growth factor receptor–targeted drug cetuximab in 80 patients. The results of these studies… 
Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?
TLDR
An overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels is given.
Stromal gene expression defines poor-prognosis subtypes in colorectal cancer
TLDR
It is shown that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progression, and all poor-prognosis CRC subtypes share a gene program induced by T GF-β in tumor stromal cells.
Molecular subtypes of colorectal cancer in pre-clinical models show differential response to targeted therapies: Treatment implications beyond KRAS mutations
TLDR
The results suggest that inhibition of pERK is a critical node in decreasing cell viability of stem-like CRC tumors and that CRC molecular subtypes may yield predictive information and may help to identify patients who may respond to targeted inhibitors.
Consensus Molecular Subtypes of Colorectal Cancer and their Clinical Implications.
TLDR
The colorectal cancer (CRC) Subtyping Consortium has unified six independent molecular classification systems into a single consensus system with four distinct groups, known as the Consensus Molecular Subtypes (CMS).
Prognosis and Therapeutic Implications for Emerging Colorectal Cancer Subtypes
TLDR
This paper reviews the original molecular classifications of colorectal cancer, microsatellite and chromosomal unstable tumors, and more recent attempts to characterize the disease by using intrinsic gene expression clustering methods, which identified at least three subtypes with different hypermutation, proliferation, and epithelial and mesenchymal features.
Neoadjuvant chemotherapy affects molecular classification of colorectal tumors
TLDR
It is concluded that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.
The prognostic value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers
TLDR
The biologically relevant and poor prognostic stem-like group could also be identified in early stage I cancers, suggesting a potential opportunity for the identification of aggressive tumors at a very early stage of the disease.
Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies
TLDR
A new, cancer cell–adapted classifier was found to perform well in primary tumors, and applied to a panel of 148 cell lines and 32 PDXs, these colorectal cancer models were shown to recapitulate the biology of the CMS groups.
Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes.
TLDR
Molecular subtype-based stratification to guide therapeutic decisions is a promising new strategy that might overcome the shortcomings of single gene testing in colorectal cancer as well as in other malignancies.
...
...

References

SHOWING 1-10 OF 43 REFERENCES
Subtypes of Pancreatic Ductal Adenocarcinoma and Their Differing Responses to Therapy
TLDR
Three PDA subtypes are defined: classical, quasimesenchymal and exocrine-like, and evidence for clinical outcome and therapeutic response differences between them is presented, and gene signatures for these subtypes that may have utility in stratifying patients for treatment are defined.
Molecular classification of prostate cancer using curated expression signatures
TLDR
A microarray dataset characterizing 281 prostate cancers from a Swedish watchful-waiting cohort provided useful unique molecular profiles for prostate cancer prognosis, helping to predict poor outcome in patients with low or average Gleason scores.
Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior
TLDR
Novel molecular subtypes in colon cancer with distinctbiological and clinical behavior that are established from the initiation of the tumor are identified.
Subtype and pathway specific responses to anticancer compounds in breast cancer
Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
  • M. Del RioF. Molina M. Ychou
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2007
TLDR
After validation in an independent cohort of patients, the gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Deciphering cellular states of innate tumor drug responses
TLDR
Molecular interaction networks are described that provide a solid foundation on which to anchor working hypotheses about mechanisms underlying in vivo innate tumor drug responses, and represent a starting point from which by-pass chemotherapy schemes may be developed for critical therapeutic intervention in CRC patients.
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer
TLDR
Metastasis-associated gene expression changes can be used to refine traditional outcome prediction, providing a rational approach for tailoring treatments to subsets of patients.
Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
TLDR
Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphireGulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment.
Single-cell dissection of transcriptional heterogeneity in human colon tumors
TLDR
It is demonstrated that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity.
...
...