Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma [In the Spotlight]
Summary: Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell renal cell carcinoma (ccRCC). In this issue of Cancer Discovery, Gu and colleagues model these genetic events in mice and report that dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. C...
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Authors: Leung, J. Y., Kim, W. Y. Tags: In the Spotlight Source Type: research
Refining Targeted Therapy Opportunities for BRAF-Mutant Melanoma [In the Spotlight]
Summary: Identifying molecular and cellular features associated with resistance to targeted BRAF/MAPK pathway inhibition may guide development of novel therapeutic approaches. Integrated, comparative analysis of genomic and functional data in sensitive and resistant cell lines unveils novel targetable regulators of resistance to MAPK pathway inhibition in melanoma. Cancer Discov; 7(8); 799–801. ©2017 AACR.
See related article by Eskiocak et al., p. 832. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Authors: Jenkins, R. W., Barbie, D. A. Tags: In the Spotlight Source Type: research
The GENIE Is Out of the Bottle: Landmark Cancer Genomics Dataset Released [In the Spotlight]
Summary: In this issue of Cancer Discovery, an overview of the AACR Project GENIE, a landmark study in cancer genomics, is presented by The AACR Project GENIE Consortium. A summary of the goals and objectives of this ambitious program is provided, together with an analysis of the phase I cohort of 19,000 samples. Cancer Discov; 7(8); 796–8. ©2017 AACR.
See related article by The AACR Project GENIE Consortium, p. 818. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Authors: Litchfield, K., Turajlic, S., Swanton, C. Tags: In the Spotlight Source Type: research
MLL2 Promotes Cell Survival in MLL1-Rearranged Acute Myeloid Leukemia [Leukemia]
Loss of MLL2, but not MLL1, suppresses MLL1-rearranged acute myeloid leukemia. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Leukemia Source Type: research
ILF2 Is Upregulated by 1q21 Amplification in Multiple Myeloma [Multiple Myeloma]
ILF2 induces resistance to DNA-damaging agents by enhancing splicing of DNA damage response mRNAs. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Multiple Myeloma Source Type: research
The FLT3 Inhibitor Gilteritinib Has Activity in Patients with AML [Clinical Trials]
Gilteritinib was well tolerated in a phase I/II dose-escalation and dose-expansion study. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Clinical Trials Source Type: research
BET Degradation Is More Effective Than Competitive Inhibition in T-ALL [Transcriptional Regulation]
The BET degrader dBET6 induces global BRD4 depletion, whereas JQ1 preferentially affects superenhancers. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Transcriptional Regulation Source Type: research
mTORC2 Regulates the Cystine-Glutamate Antiporter xCT [Metabolism]
mTORC2 controls glutamate and glutathione metabolism in cancer cells by phosphorylating xCT. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Metabolism Source Type: research
BAP1 and PTEN Stabilize IP3R3 to Promote Ca2+-Mediated Apoptosis [Apoptosis]
BAP1 and PTEN prevent IP3R3 degradation, increasing Ca2+ flux and apoptosis to suppress tumor growth. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Apoptosis Source Type: research
A Subset of Gene Promoters Exhibit Both Promoter and Enhancer Activity [Gene Expression]
Approximately 2%–3% of gene promoters also display distal enhancer activity (termed Epromoters). (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Gene Expression Source Type: research
De Novo Methylation Halts PD-1 Blockade-Mediated T-cell Revitalization [Immunology]
Heritable de novo methylation programs induce the terminal differentiation of exhausted T cells. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Immunology Source Type: research
A Click-Chemistry Approach Reveals the BET Inhibitor Mechanism of Action [Drug Evaluation]
Click chemistry–based modification of BET inhibitors allows use as molecular probes in vitro and in vivo. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Drug Evaluation Source Type: research
Mismatch-Repair Deficiency Confers Sensitivity to Checkpoint Blockade [Clinical Trials]
PD-1 blockade with pembrolizumab achieves responses in 53% of patients with MMR-deficient tumors. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: Clinical Trials Source Type: research
Noted [News in Brief]
A collection of recently published news items. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: News in Brief Source Type: research
Dual HER2 Blockade Helps Prevent Breast Cancer Return [News in Brief]
Adding pertuzumab to an adjuvant regimen of trastuzumab for women with early-stage HER2+ breast cancer reduces the risk of disease recurrence, especially among those with node-positive and hormone receptor–negative disease. Results from the phase III APHINITY trial, which could help pertuzumab earn full approval for this indication, were presented at the 2017 American Society of Clinical Oncology Annual Meeting. (Source: Cancer Discovery)
Source: Cancer Discovery - August 1, 2017 Category: Cancer & Oncology Tags: News in Brief Source Type: research
