Spotlight on Ibrutinib in PCNSL: Adding Another Feather to Its Cap [In the Spotlight]
Summary: In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the central nervous system. Mutations in the B-cell antigen receptor–associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing op...
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Authors: Lakshmanan, A., Byrd, J. C. Tags: In the Spotlight Source Type: research
Reversion Mutations with Clinical Use of PARP Inhibitors: Many Genes, Many Versions [In the Spotlight]
Summary: Reversion mutations associated with PARP inhibitor resistance have been identified in tumors with RAD51C, RAD51D, and PALB2 as well as BRCA1 and BRCA2 mutations. Multiple different reversion mutations can occur in a single patient, and they can be detected by analysis of circulating cell-free DNA. Cancer Discov; 7(9); 937–9. ©2017 AACR.
See related article by Kondrashova et al., p. 984.
See related article by Quigley et al., p. 999.
See related article by Goodall et al., p. 1006. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Authors: Domchek, S. M. Tags: In the Spotlight Source Type: research
Fast-TRKing Drug Development for Rare Molecular Targets [In the Spotlight]
Summary: Drug development for rare molecular targets in oncology presents unique challenges. In this issue of Cancer Discovery, Drilon and colleagues report the accelerated development and innovative initial clinical trial strategy of a next-generation TRK inhibitor, LOXO-195, designed to overcome common secondary TRK resistance mutations. Cancer Discov; 7(9); 934–6. ©2017 AACR.
See related article by Drilon et al., p. 963. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Authors: Parikh, A. R., Corcoran, R. B. Tags: In the Spotlight Source Type: research
Frameshift Indels Generate Highly Immunogenic Tumor Neoantigens [Tumor Antigens]
Renal clear cell carcinomas have the highest proportion of indels, which are linked to immune activation. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Tumor Antigens Source Type: research
BAX Can Be Allosterically Sensitized to Promote Apoptosis [Apoptosis]
An NMR-based fragment screen identified a BAX-interacting compound, BIF-44, that enhances BAX activity. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Apoptosis Source Type: research
Core Regulatory Circuitries Mediate Neuroblastoma Heterogeneity [Neuroblastoma]
Sympathetic noradrenergic and NCC-like transcriptional networks promote neuroblastoma heterogeneity. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Neuroblastoma Source Type: research
PTPN2 Loss Sensitizes Tumor Cells to Immunotherapy [Immunotherapy]
Ptpn2 loss increases tumor cell IFN signaling to enhance antigen presentation and antitumor immunity. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Immunotherapy Source Type: research
ASCL1 Promotes Differentiation of Glioblastoma Stem Cells [Glioblastoma]
ASCL1 promotes neuronal gene expression to induce differentiation and suppress glioblastoma growth. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Glioblastoma Source Type: research
Simultaneous Targeting of RAF, MEK, and ERK Limits Drug Resistance [Kinase Inhibitors]
Sequential targeting of RAF, MEK, or ERK in BRAF-mutant PDXs promotes BRAF amplification and resistance. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Kinase Inhibitors Source Type: research
Fusobacterium nucleatum Promotes Autophagy-Mediated Chemoresistance [Drug Resistance]
Abundant F. nucleatum is associated with disease recurrence in patients with colorectal cancer. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Drug Resistance Source Type: research
Nivolumab Has Antitumor Activity in dMMR/MSI-H Colorectal Cancer [Clinical Trials]
Nivolumab is safe and achieves durable responses in metastatic dMMR/MSI-H colorectal cancer. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Clinical Trials Source Type: research
Chromosome Loop Anchors Are Susceptible to DNA Double-Strand Breaks [Translocations]
TOP2B induces double-strand breaks at CTCF-bound DNA loop anchors, increasing genomic rearrangements. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Translocations Source Type: research
The Telomeric Noncoding RNA TERRA Regulates Telomere Stability [Telomeres]
TERRA activates the DNA damage response at short telomeres to prevent premature senescence. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: Telomeres Source Type: research
Taking the Guesswork Out of Stopping TKIs [News in Depth]
More and more patients with chronic myeloid leukemia are discontinuing therapy after their cancer goes into remission, improving their quality of life and remaining disease-free for years. However, this strategy works only in a subset of patients. Researchers are attempting to refine criteria for discontinuing treatment, determine the manner in which therapy should be stopped, and identify prognostic biomarkers. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: News in Depth Source Type: research
Why First-Line Nivolumab Is No Better than Chemo [News in Depth]
In a recent trial, the PD-1 inhibitor nivolumab failed to outperform chemotherapy as a first-line treatment for non–small cell lung cancer, even though another PD-1 inhibitor, pembrolizumab, was shown to be an effective treatment just months earlier. Researchers attribute these surprising results to differences in patient selection in the two trials, and suggest that the discovery of better biomarkers, among other strategies, might allow more patients to benefit from immunotherapies. (Source: Cancer Discovery)
Source: Cancer Discovery - August 31, 2017 Category: Cancer & Oncology Tags: News in Depth Source Type: research
