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Cancer Discovery
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26.37
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Papers 1193
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#1Cécile K. Lopez (French Institute of Health and Medical Research)H-Index: 8
#2Esteve Noguera (French Institute of Health and Medical Research)
Last.Thomas Mercher (French Institute of Health and Medical Research)H-Index: 25
view all 36 authors...
Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, like ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia while expression in adult bone marrow hem...
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#2Jill HallinH-Index: 6
Last.Peter Olson (Pfizer)H-Index: 11
view all 34 authors...
Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C and inhibits KRAS-dependent signaling. MRTX849 demonstrated pronounced tumor regression in 17 of 26 (65%) of KRASG12C-positive cell line- and patient-derived xenograft models from multiple tumor types and objective responses have...
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#1G. Aaron Hobbs (UNC: University of North Carolina at Chapel Hill)H-Index: 9
#2Nicole M. Baker (UNC: University of North Carolina at Chapel Hill)H-Index: 4
Last.Channing J. Der (UNC: University of North Carolina at Chapel Hill)H-Index: 107
view all 28 authors...
Allele-specific signaling by different KRAS alleles remains poorly understood. The KRASG12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: it is rare in lung and colorectal cancers (~1%), yet relatively common (~20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRASG12R is functionally distinct from the more common KRASG12D or KRASG12V mutant proteins (KRASG12D/V). We found that K...
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#1Esther A. Obeng (St. Jude Children's Research Hospital)H-Index: 6
#2Connor Stewart (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last.Omar Abdel-Wahab (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 68
view all 3 authors...
Major advances in our understanding of cancer pathogenesis and therapy have come from efforts to catalog genomic alterations in cancer. A growing number of large-scale genomic studies have uncovered mutations that drive cancer by perturbing cotranscriptional and post-transcriptional regulation of gene expression. These include alterations that affect each phase of RNA processing, including splicing, transport, editing, and decay of messenger RNA. The discovery of these events illuminates a numbe...
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#1Remi Klotz (SC: University of Southern California)
#2Amal Thomas (SC: University of Southern California)H-Index: 2
Last.Min Yu (SC: University of Southern California)H-Index: 21
view all 27 authors...
Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTCs) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived and expanded ex vivo from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from breast c...
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#1Carlotta Costa (Novartis)H-Index: 1
#2Ye Wang (Novartis)
Last.Dejan Juric (Harvard University)H-Index: 29
view all 25 authors...
The combination of CDK4/6 inhibitors with anti-estrogen therapies significantly improves clinical outcomes in ER-positive advanced breast cancer. To identify mechanisms of acquired resistance, we analyzed serial biopsies and rapid autopsies from patients treated with the combination of the CDK4/6 inhibitor ribociclib with letrozole. This study revealed that some resistant tumors acquired RB loss, whereas other tumors lost PTEN expression at the time of progression. In breast cancer cells ablatio...
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#1Yun-Han Huang (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2Jing Hu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last.Joan Massagué (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 176
view all 12 authors...
TGF-β is an important tumor suppressor in pancreatic ductal adenocarcinoma (PDA), yet inactivation of TGF-β pathway components occurs in only half of PDA cases. TGF-β cooperates with oncogenic RAS signaling to trigger epithelial-mesenchymal transition (EMT) in pre-malignant pancreatic epithelial progenitors, which is coupled to apoptosis owing to an imbalance of SOX4 and KLF5 transcription factors. We report that PDAs that develop with the TGF-β pathway intact avert this apoptotic effect via Inh...
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#1YongKang Zou (Wistar Institute)
#2Andrea Watters (Wistar Institute)H-Index: 4
Last.Qing Chen (Wistar Institute)H-Index: 1
view all 16 authors...
Brain metastasis, the most ominous form of melanoma and carcinoma, is the consequence of favorable interactions between the invaded cancer cells and the brain cells. Peroxisome proliferator-activated receptor gamma (PPAR gamma has ambiguous functions in cancer development and its relevance in advanced brain metastasis remains unclear. Here, we demonstrate that astrocytes, the unique brain glia cells, activate PPAR gamma in brain metastatic cancer cells. PPAR gamma activation enhances cell prolif...
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#1Jay F. Sarthy (Seattle Children's)H-Index: 2
#2Steven Henikoff (Fred Hutchinson Cancer Research Center)H-Index: 89
Summary: Identification of cancer-associated mutations in core histone genes has proved challenging due to these genes9 highly conserved nature and presence in large arrays. Recent analyses of cancer genomes, including one in this issue of Cancer Discovery, show that mutations in the histone fold can affect nucleosome stability, providing a novel mechanism by which oncohistones contribute to tumorigenesis. See related article by Bennett et al., p. 1438.
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#1Anna F. Farago (Harvard University)H-Index: 21
#2Beow Y. Yeap (Harvard University)H-Index: 64
Last.Benjamin J. Drapkin (Harvard University)H-Index: 7
view all 25 authors...
Small cell lung cancer (SCLC) is an aggressive malignancy in which inhibitors of poly (ADP-ribose) polymerase (PARP) have modest single-agent activity. We performed a phase I/II trial of combination olaparib tablets and temozolomide (OT) in previously treated SCLC. We established a recommended phase 2 dose (RP2D) of olaparib 200 mg PO BID with temozolomide 75 mg/m2 daily, both on days 1-7 of a 21-day cycle, and expanded to a total of 50 patients. The confirmed overall response rate (ORR) was 41....
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