TY - JOUR
T1 - Genomically driven tumors and actionability across histologies
T2 - BRAF-mutant cancers as a paradigm
AU - Turski, Michelle L.
AU - Vidwans, Smruti J.
AU - Janku, Filip
AU - Garrido-Laguna, Ignacio
AU - Munoz, Javier
AU - Schwab, Richard
AU - Subbiah, Vivek
AU - Rodon, Jordi
AU - Kurzrock, Razelle
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/4
Y1 - 2016/4
N2 - The diagnosis, classification, and management of cancer are traditionally dictated by the site of tumor origin, for example, breast or lung, and by specific histologic subtypes of site-oforigin cancers (e.g., non-small cell versus small cell lung cancer). However, with the advent of sequencing technologies allowing for rapid, low cost, and accurate sequencing of clinical samples, new observations suggest an expanded or different approach to the diagnosis and treatment of cancer-one driven by the unique molecular features of the tumor. We discuss a genomically driven strategy for cancer treatment using BRAF as an example. Several key points are highlighted: (i) molecular aberrations can be shared across cancers; (ii) approximately 15% of all cancers harbor BRAF mutations; and (iii) BRAF inhibitors, while approved only for melanoma, have reported activity across numerous cancers and related disease types bearing BRAF aberrations. However, BRAF-mutated colorectal cancer has shown poor response rate to BRAF inhibitor monotherapy, striking a cautionary note. Yet, even in this case, emerging data suggest BRAF-mutated colorectal cancers can respond well to BRAF inhibitors, albeit when administered in combination with other agents that impact resistance pathways. Taken together, these data suggest that molecular aberrations may be the basis for a new nosology for cancer.
AB - The diagnosis, classification, and management of cancer are traditionally dictated by the site of tumor origin, for example, breast or lung, and by specific histologic subtypes of site-oforigin cancers (e.g., non-small cell versus small cell lung cancer). However, with the advent of sequencing technologies allowing for rapid, low cost, and accurate sequencing of clinical samples, new observations suggest an expanded or different approach to the diagnosis and treatment of cancer-one driven by the unique molecular features of the tumor. We discuss a genomically driven strategy for cancer treatment using BRAF as an example. Several key points are highlighted: (i) molecular aberrations can be shared across cancers; (ii) approximately 15% of all cancers harbor BRAF mutations; and (iii) BRAF inhibitors, while approved only for melanoma, have reported activity across numerous cancers and related disease types bearing BRAF aberrations. However, BRAF-mutated colorectal cancer has shown poor response rate to BRAF inhibitor monotherapy, striking a cautionary note. Yet, even in this case, emerging data suggest BRAF-mutated colorectal cancers can respond well to BRAF inhibitors, albeit when administered in combination with other agents that impact resistance pathways. Taken together, these data suggest that molecular aberrations may be the basis for a new nosology for cancer.
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U2 - 10.1158/1535-7163.MCT-15-0643
DO - 10.1158/1535-7163.MCT-15-0643
M3 - Review article
C2 - 27009213
AN - SCOPUS:84964334401
SN - 1535-7163
VL - 15
SP - 533
EP - 547
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 4
ER -