Acute Myelogenous Leukemia
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  • ||||||||||  LY294002 / Eli Lilly
    Journal, IO biomarker:  miR-149-3p Enhances Drug Sensitivity of AML Cells by Inhibiting Warburg Effect Through PI3K/AKT Pathway. (Pubmed Central) -  Nov 19, 2024   
    regulating chemotherapy resistance of AML cells through Warburg effect...Upregulation of miR-149-3p expression may potentially be a therapeutic target for AML resistance. It has been shown to inhibit PI3K/AKT pathway activation, thereby inhibiting the Warburg effect, and affecting cell proliferation, apoptosis, and drug resistance.
  • ||||||||||  Review, Journal, IO biomarker:  Immunophenotypic features of early haematopoietic and leukaemia stem cells. (Pubmed Central) -  Nov 19, 2024   
    In acute myeloid leukaemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as an addition to measurable residual disease. However, challenges such as the CD34-negative immunophenotype need to be explored.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Review, Journal, IO biomarker:  Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead. (Pubmed Central) -  Nov 19, 2024   
    Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.
  • ||||||||||  Review, Journal, CAR T-Cell Therapy:  Evolving strategies to overcome barriers in CAR-T cell therapy for acute myeloid leukemia. (Pubmed Central) -  Nov 19, 2024   
    This review will focus on these barriers to successful CAR-T cell therapy in AML, and discuss scientific advancements and evolving strategies to overcome them. Achieving durable remissions in R/R AML will likely require a multifaceted approach that integrates advancements in TTA selection, enhancement of the intrinsic quality of CAR-T cells, and development of strategies to overcome inhibitory mechanisms in the AML TME.
  • ||||||||||  Zeltherva (galinpepimut-S) / SELLAS Life Sciences
    Trial completion, Enrollment change, Combination therapy, Metastases:  Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers (clinicaltrials.gov) -  Nov 19, 2024   
    P1/2,  N=26, Completed, 
    Achieving durable remissions in R/R AML will likely require a multifaceted approach that integrates advancements in TTA selection, enhancement of the intrinsic quality of CAR-T cells, and development of strategies to overcome inhibitory mechanisms in the AML TME. Active, not recruiting --> Completed | N=90 --> 26
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Trial completion date, Trial primary completion date:  CAV Regimen for R/R AML (clinicaltrials.gov) -  Nov 19, 2024   
    P2,  N=68, Recruiting, 
    Active, not recruiting --> Completed | N=90 --> 26 Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Review, Journal:  BCL-2 inhibition in acute myeloid leukemia: resistance and combinations. (Pubmed Central) -  Nov 18, 2024   
    This review aims to elucidate the primary mechanisms underlying resistance to venetoclax and explore current therapeutic strategies to overcome this challenge.Expert opinion: In patients with venetoclax resistance, alternative options include targeted combination therapies tailored to individual cases based on cytogenetics and prior treatments. Many of these therapies require further clinical investigation to validate their safety and efficacy.
  • ||||||||||  chlorthalidone / Generic mfg., telmisartan / Generic mfg.
    Enrollment open, Trial completion date, Trial primary completion date, Head-to-Head:  Study to Evaluate the Efficacy and Safety of TEL/AML/CTD in Elderly Patients with Essential Hypertension (clinicaltrials.gov) -  Nov 18, 2024   
    P4,  N=250, Recruiting, 
    In summary, grade 2-3 MF in AML is associated with worse outcomes. Not yet recruiting --> Recruiting | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Feb 2025 --> Jun 2025
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Dendrobium nobile Lindl. alkaloids protect CCl4-induced acute liver injury via upregulating LAMP1 expression and activating autophagy flux. (Pubmed Central) -  Nov 17, 2024   
    While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl4 induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage.
  • ||||||||||  Journal, IO biomarker:  A line in shifting sand: Can we define and target TP53 mutated MDS? (Pubmed Central) -  Nov 17, 2024   
    Our current understanding is that TP53 mutated MDS and AML are globally quite similar, but as a group have unique features compared to TP53 wildtype (WT) disease. Optimizing immunotherapy and targeting vulnerabilities due to co-mutations and/or chromosome abnormalities should be the focus of future research.
  • ||||||||||  Journal:  RNA splicing as a therapeutic target in myelodysplastic syndromes. (Pubmed Central) -  Nov 17, 2024   
    Emerging evidence shows that splicing factor-mutant cells are more sensitive to perturbations targeting the spliceosome, aberrantly spliced genes and/or their regulated molecular pathways. This review summarizes current therapeutic strategies and ongoing efforts targeting splicing factor mutations for the treatment of MDS.
  • ||||||||||  Journal, Patient reported outcomes:  Patient-reported outcomes in early phase trials for patients with myelodysplastic syndromes. (Pubmed Central) -  Nov 17, 2024   
    We will provide a general overview of PROs and follow with application of PROs in MDS/AML including strategies to be considered in early phase trials. Finally, we describe the creation of the Office of Patient-Centered Outcomes Research at the US National Institutes of Health which has developed a standardized PROs methodology for early phase trials conducted in the Center for Cancer Research at the US National Cancer Institute.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Review, Journal:  Breaking down frailty: Assessing vulnerability in acute myeloid leukemia. (Pubmed Central) -  Nov 16, 2024   
    Lack of consensus exists on how to select older, less fit patients most appropriate for standard intensive chemotherapy (IC), hypomethylating agents (HMA) with venetoclax, or less intensive regimens...CGA, Geriatric 8 (G8) risk score, and hematopoietic cell transplant comorbidity index (HCT-CI) show association with prognosis, and should be validated in larger therapeutic trials. Studies of biomarkers, like albumin and C-reactive protein, and patient-reported outcomes demonstrate the potential to enhance information gained from rigorous geriatric assessment.
  • ||||||||||  Review, Journal:  PEComas: A review of imaging and clinical features. (Pubmed Central) -  Nov 16, 2024   
    Some PEComas are benign and easily resected while others may represent systemic or metastatic disease with limited therapeutic options. The purpose of this review is to introduce the topic of perivascular epithelioid cell tumors and the most common tumors within the PEComa family as well as discuss the epidemiology, morphology, radiographic appearance, and treatment options of these rare tumors.