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Mashup Score: 3
In a phase II basket trial, the BRAF inhibitor vemurafenib showed preliminary evidence of efficacy in 13 BRAF-mutant non-melanoma tumor types, including some typically considered treatment refractory.
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 0Targeting Alterations in the RAF–MEK Pathway - 4 hour(s) ago
AbstractThe MAPK pathway is one of the most commonly mutated oncogenic pathways in cancer. Although RAS mutations are the most frequent MAPK alterations, less frequent alterations in downstream components of the pathway, including the RAF and MEK genes, offer promising therapeutic opportunities. In addition to BRAFV600 mutations, for which several approved therapeutic regimens exist, other alterations in the RAF and MEK genes may provide more rare, but tractable, targets. However, recent studies have illustrated the complexity of MAPK signaling and highlighted that distinct alterations in these genes may have strikingly different properties. Understanding the unique functional characteristics of specific RAF and MEK alterations, reviewed herein, will be critical for developing effective therapeutic approaches for these targets.Significance:. Alterations in the RAF and MEK genes represent promising therapeutic targets in multiple cancer types. However, given the unique and complex signa
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2
Abstract. The European Society for Medical Oncology defines rare cancers as 5 or fewer cases per 100,000 persons per year. For many rare cancers, no standard of care exists, and treatment is often extrapolated. Identifying potentially targetable genomic alterations in rare tumors is a rational approach to improving treatment options. We sought to catalog these mutations in rare tumors and to assess their clinical utility.For this retrospective analysis, we selected rare tumor patients from a dataset of patients who underwent clinical tumor genomic profiling. Sarcomas were excluded. To index potentially actionable alterations, patients’ reports were reviewed for mutations in cancer-associated genes and pathways. Respective clinical records were abstracted to appraise the benefit of using a targeted therapy approach. Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials.The 95 patients analyzed had 40 different tumor subtypes, most
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet-
Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers [Apr 13, 2018] @RGroisberg et al @VivekSubbiah @MCT_AACR https://t.co/L4Qnl7XGhi #PrecisionMedicine 36/95 (38%) >=1 potentially actionable target; 13/95 (14%) received targeted Tx (pragmatic actionability) https://t.co/7ZdyJsYbfk
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Mashup Score: 3Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma - 20 hour(s) ago
Abstract. PURPOSE: Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. EXPERIMENTAL DESIGN: Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies (NCT01572480, NCT02279394). RESULTS: We reveal that the genomic landscape of treated HR-SMM is generally simple as compared to Newly Diagnosed (ND)MM counterparts with less inactivation of tumor suppressor genes, RAS pathway mutations, MYC disruption, and APOBEC contribution. The absence of these events parallels that of indolent precursor conditions, possibly explaining overall excellent outcomes. However, some patients harboring genomic complexity fail to sustain response and experience resistant, progressive disease. Overall, clinical risk scores do not effectively discrim
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2Understanding Academic Medical Centers: Simone’s Maxims - 1 day(s) ago
Academic medical centers today represent a unique fusion of traditional academia, hospital functions, several levels of education, and, above all, patients. They are complex organizations trying to discharge an often conflicting melange of responsibilities. This complexity has grown in recent years with the increasingly rapid rate of change (1), stressing both faculty and leadership (2, 3). Lamenting the toll of change is not new (4). However, the qualitative difference in recent change is underscored by the shift in focus of two articles, 15 years apart, on academic governance by Petersdorf (5, 6), especially as they have affected deans and their dramatically shrinking tenures. Economic turmoil and its consequences are blamed most often for the angst in academic medical centers (7). And yet, some blame the faculty and leadership for not changing fast enough (8) or for choosing doomed strategic pathways in response to those pressures (9). In fact, a Forum on the Future of Academic Medi
Source: aacrjournals.orgCategories: General Medicine News, General HCPsTweet
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Mashup Score: 24
Abstract. Several second- and third-line immunotherapeutic options for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant are directed against the B-cell antigen CD19. The anti-CD19 monoclonal antibody tafasitamab, paired with the immunomodulator lenalidomide, mediates antibody-dependent cellular toxicity and cellular phagocytosis; the antibody–drug conjugate loncastuximab tesirine delivers the DNA-cross-linking agent tesirine via CD19 binding and internalization; and CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) products are engineered from autologous T cells. While CD19 expression is assessed at diagnosis, clinically relevant thresholds of CD19 expression—which may not be detectable with current routine methodologies—have not been defined and may vary between CD19-directed treatment modalities. Determining optimal treatment sequencing strategies with CD19-directed therapy has been hampered by the
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 0Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case–Control Study in Iran - 2 day(s) ago
AbstractBackground:. Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern.Methods:. We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer.Results:. We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69–1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16–2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21–4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 36Germline Testing identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors - 3 day(s) ago
Abstract. 10% of pancreatic neuroendocrine tumors (pNETs) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathological/likely pathological germline variants (P/LP) in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center (MDACC) and Johns Hopkins Hospital (JHH). High-risk cohort included (n=132) patients seen at MDACC who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer and syndromic features) between 2013-2019. Unselected cohort (n=106) patients seen at JHH who underwent germline testing following their diagnosis of pNETs between 2020 to 2022. In the high-risk cohort (n=132), 33% (n=44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n=25), followed by DNA repair pathway
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet-
In @CAPR_AACR from @hopkinskimmel & @MDAndersonNews #PancreaticCancer teams: Germline Testing identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors https://t.co/PPLsGC8wT4 In an unselected population, 1 in 5 harbor germline alterations… https://t.co/nb8IGxwIbU
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Mashup Score: 0
Convergence Science | Cancer Research | American Association for Cancer Research .aacrcontent { display: flex; flex-direction: row; justify-content: space-between; align-items: stretch; } .intro { margin-top: 26px; font-size: 1.2em; } /* ****************** LEFT SIDE ****************** */ .left-side{ color: #000000; background-color: #fff; max-width: 710px; margin-right: 26px; } .left-side h3{ margin-bottom: 26px; } .node { line-height: 1.2em; margin-left: 12px; } .node2 {line-height: 1.0em; }…
Source: aacrjournals.orgCategories: General Medicine News, Onc News and JournalsTweet
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Mashup Score: 0
Targeted degradation of EP300 with a novel PROTAC agent in neuroblastoma cells was found to cause widespread loss of gene expression and cell death in vitro and in vivo.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers [February 6, 2020] @VivekSubbiah et al. @CD_AACR https://t.co/5Aj0rjb5xN @AACR #PrecisionMedicine