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Mashup Score: 2Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism - 1 day(s) ago
Abstract. Most aggressive lymphomas are treated with combination chemotherapy, commonly as multiple cycles of concurrent drug administration. Concurrent administration is in theory optimal when combination therapies have synergistic (more than additive) drug interactions. We investigated pharmacodynamic interactions in the standard 4-drug “CHOP” regimen in peripheral T-cell lymphoma (PTCL) cell lines and found that CHOP consistently exhibits antagonism and not synergy. We tested whether staggered treatment schedules could improve tumor cell kill by avoiding antagonism, using in vitro models of concurrent or staggered treatments. Surprisingly, we observed that tumor cell kill is maximized by concurrent drug administration despite antagonistic drug–drug interactions. We propose that an ultrasensitive dose response, as described in radiology by the linear–quadratic (LQ) model, can reconcile these seemingly contradictory experimental observations. The LQ model describes the relationship be
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 18YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer - 1 day(s) ago
YAP1 regulates cancer-associated fibroblast phenotypes and can be targeted to switch cancer-associated fibroblasts from a protumorigenic subtype that promotes extracellular matrix deposition to a tumor-suppressive subtype that stimulates antitumor immunity and immunotherapy efficacy.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 7
m6A epitranscriptome profiling analysis of lung adenocarcinoma and non-neoplastic lung identifies EML4 as a hyper-methylated metastatic driver and a promising therapeutic target to prevent lung adenocarcinoma metastasis.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 2Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma - 2 day(s) ago
Abstract. Low intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogeneous tumors are variably aggressive, and the immunological factors impacting aggressiveness remain understudied. Here, we analyzed the mechanisms underlying immune escape in murine tumors with low ITH. We used immunophenotyping and single-cell RNA sequencing to compare the temporal growth of in-vivo transplanted, genetically similar rejected vs. non-rejected single-cell clones. Non-rejected clones showed high infiltration of tumor-associated macrophages (TAMs), lower T-cell infiltration, and increased T-cell exhaustion compared to rejected clones. Comparative analysis of rejection-associated gene expression programs, combined with in-vivo CRISPR knockout screens of candidate regulators, identified Mif (macrophage migration inhibitory factor) as a major contributor to immune rejection. Mif knockout resulted in smaller tumors and reduced TAM inf
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet-
New @CD_AACR study from @samuels_yardena (with @NCIEytanRuppin @Satpathology et al) Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma https://t.co/blIiFOy1bf Even so-called homogeneous tumors have intrinsic heterogeneity… https://t.co/xkom4qy1qY
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Mashup Score: 1Pembrolizumab Shot on Par with IV - 2 day(s) ago
Merck announced today that pembrolizumab (Keytruda) injected subcutaneously is not inferior to intravenous (IV) dosing, currently the drug’s only approved route of administration. In the phase III MK-3475A-D77 trial, researchers found that patients with metastatic non–small cell lung cancer who received pembrolizumab plus chemotherapy had similar blood plasma concentrations of the PD-1 inhibitor regardless of how it was given. Detailed results will be presented at an upcoming medical meeting and shared with regulatory authorities. Merck’s patent on IV pembrolizumab, which generated $25 billion in sales in 2023, will expire in 2028, but the subcutaneous form of the drug would extend its patent protection.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 1DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma - 2 day(s) ago
The RNA-binding protein DAZAP1 undergoes phase separation to enhance COX16 expression and mediate metabolic reprogramming that enables tumor metastasis, highlighting DAZAP1 as a potential metabolic target for cancer therapy.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 0BMS Hit with Renewed, Massive Lawsuit - 2 day(s) ago
Bristol Myers Squibb (BMS) faces a $6.7 billion lawsuit alleging that the company purposely delayed approval of Celgene-developed drugs to avoid paying Celgene shareholders owning contingent value rights (CVR), according to Reuters. An earlier suit, brought for $6.4 billion, was dismissed in late September on the grounds that the plaintiff, UMB Bank, was never properly appointed to represent the owners of CVRs and therefore lacked standing. CVRs are awarded to shareholders of a company being acquired; when BMS acquired Celgene in 2019, it guaranteed investors an additional payout pending FDA approval of three Celgene drugs, but the approval deadline was not met for lisocabtagene maraleucel (Breyanzi), a gene therapy for non-Hodgkin lymphoma. UMB Bank said it had addressed the judge’s concerns and been confirmed as a trustee, enabling the suit to proceed.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 0The Context of Poverty and Cancer: Denying Human Potential - 2 day(s) ago
Abstract. Poverty is a carcinogen and a leading cause of cancer disparities and overall mortality in the United States. Poverty is often viewed as an individual failure for “being poor,” but in fact, poverty is structurally driven, intergenerational, and place-based that socially deprives and denies human potential. Disparities in timely cancer prevention, diagnosis, treatment, survivorship, and survival disproportionally impact people living in poverty and especially in persistent poverty areas, an extreme form of place-based poverty that affects communities over multiple generations. There has been some progress made to address place-based conditions that exacerbate poverty, such as the NCI’s initiative on persistent poverty. However, gross inequality and cancer disparities continue to exist and persist. The time is now to accelerate the development of research-informed strategies and solutions with communities along with multisectoral collaborations with education, housing, occupati
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 1Targeting Noncoding cis-Regulatory Elements for Cancer Therapy in the Context of the 3D Genome - 2 day(s) ago
Summary:. Significant efforts have been made to identify and validate oncoproteins and ncRNAs as therapeutic targets for cancer therapy; however, emerging observations suggest that noncoding cis-regulatory elements, which orchestrate the 3D organization of the genome and thus the transcriptional landscape, are potential therapeutic targets as well. In this commentary, we envisage that further efforts to decipher the noncoding cis-regulatory code and performing systematic surveys of functional noncoding cis-regulatory elements and recurrent 3D genome alterations in both cancerous and nonmalignant cells within tumor tissues will pave the way to the development of novel therapeutic strategies.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
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Mashup Score: 0
LX1 simultaneously targets androgen receptor variants and the steroidogenic enzyme AKR1C3, offering a promising approach to combat drug resistance and enhancing therapeutic efficacy in conjunction with standard treatments for advanced prostate cancer.
Source: aacrjournals.orgCategories: General Medicine News, Oncologists1Tweet
RT @mathoncbro: "Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism" https://t.co/IrXWg7KXoo…