Asparagine depleter 
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 6 Companies  5 Products   5 Products   72 Diseases   85 Trials   909 News 
  • ||||||||||  Asparaginase: Optimizing Efficacy and Minimizing Toxicity in Pediatric and AYA ALL/LBL () -  Aug 30, 2024 - Abstract #SOHO2024SOHO_1035;    
    P1
    Most patients can complete all planned asparaginase courses, given the availability of non-immunologically cross-reactive products and medical management of several common toxicities. However, challenges remain, with ongoing and future studies aimed at further improving the tolerability of asparaginase therapy.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Journal:  Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia. (Pubmed Central) -  Jun 3, 2024   
    Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy...In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.
  • ||||||||||  mercaptopurine / Generic mfg., doxorubicin hydrochloride / Generic mfg., vincristine / Generic mfg.
    POLYPHOSPHATES ARE REGULATORS OF METABOLIC HOMEOSTASIS UPON STARVATION IN DRUG RESISTANT LEUKEMIA CELLS (Poster Area (Hall 7)) -  May 15, 2024 - Abstract #EHA2024EHA_3429;    
    Collectively, we here identified polyphosphates as regulators of adaptive protein degradation, representing apreviously unknown mechanism to maintain metabolic homeostasis in leukemia cells. These results serve as astrong proponent for further analysis of polyphosphates in mediating leukemia cell fitness upon amino acidstarvation and thus provide a basis for therapeutic intervention in resistant leukemias.
  • ||||||||||  Asparlas (calaspargase pegol-mknl) / Servier, Takeda, Leadiant Biosci, Oncaspar liquid (pegaspargase) / Servier, Rylaze (recombinant Erwinia asparaginase) / Jazz
    Adverse Event Outcomes When Changing Front-line Asparaginase Products for Leukemia Patients At A Children's Hospital () -  Apr 7, 2024 - Abstract #HOPA2024HOPA_165;    
    Since August 2022, our institution has expanded therapeutic drug monitoring of long-acting asparaginase products (pegaspargase and calaspargase pegol) to include peak (1-24 hours post-infusion), 7-day post-infusion ( In December of 2022 pegaspargase (Oncospar
  • ||||||||||  Pemazyre (pemigatinib) / Incyte, Specialised Therap
    Journal:  A DNA/RNA heteroduplex oligonucleotide coupling asparagine depletion restricts FGFR2 fusion-driven intrahepatic cholangiocarcinoma. (Pubmed Central) -  Oct 24, 2023   
    Consolidation I consisted of high-dose methotrexate (A), followed by a BFM-like intensification (B), and a course of high-dose cytarabine, etoposide and dexamethasone (C)...Treatment on trial (compared to Pemigatinib, a pan-FGFR inhibitor, is approved to treat intrahepatic cholangiocarcinoma (ICC) harboring FGFR2 fusion mutations...Asn restriction with ASNase or ASNS inhibitors reduced the intracellular Asn, thereby reactivating p53
  • ||||||||||  Kidrolase (L-asparaginase) / Jazz, Merck (MSD), Erwinase (erwinia L-asparaginase) / Jazz, Ohara Pharma, Oncaspar liquid (pegaspargase) / Servier
    Journal:  Our Experiences with Asparaginase Activity Measurements in Children with Lymphoblastic Diseases. (Pubmed Central) -  Jul 29, 2023   
    activity and tolerance of asparagine starvation. Monitoring of AEA can help to identify patients with 'silent inactivation' and their asparaginase therapy can thus be optimized.
  • ||||||||||  sirolimus / Generic mfg.
    Asparagine Bioavailability Regulates the Translation of MYC oncogene in Lymphoid Malignancies (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_2140;    
    Mechanistic Target of Rapamycin Complex 1 (mTORC1) and General Controlled Nonderepressible 2 (GCN2) are the two central molecular components involved in amino acid sensing and translation control...While either of the single treatments only modestly reduced the tumor burden, the double treatment showed the most significant reduction in the tumor burden, which correlated with a significant reduction of c-MYC protein expression. These results suggest that perturbing the asparagine biosynthesis pathway can be clinically employed to inhibit c-MYC protein expression and improve therapeutic outcomes.
  • ||||||||||  Journal:  Asparagine bioavailability regulates the translation of MYC oncogene. (Pubmed Central) -  Nov 2, 2022   
    Finally, using a MYC-driven mouse B cell lymphoma model, we found that shRNA inhibition of asparagine synthetase (ASNS) or pharmacological inhibition of asparagine production can significantly reduce the MYC protein expression and tumor growth when environmental asparagine becomes limiting. Since MYC is a critical oncogene, our results uncover a molecular connection between MYC mRNA translation and asparagine bioavailability and shed light on a potential to target MYC oncogene post-transcriptionally through asparagine restriction.
  • ||||||||||  Journal:  Targeting amino acid metabolism in cancer. (Pubmed Central) -  Nov 1, 2022   
    Arginine auxotrophic tumors are great candidates for arginine-starvation therapy. Higher requirement for essential amino acids such as methionine and cysteine point out promising targetable weaknesses of cancer cells.
  • ||||||||||  Journal:  Supramolecular assembly of GSK3α as a cellular response to amino acid starvation. (Pubmed Central) -  Aug 11, 2022   
    In human leukemia, GSK3α body formation predicts asparaginase resistance, and sensitivity to asparaginase combined with a GSK3α inhibitor. We propose that GSK3α body formation provides a cellular mechanism to maximize the catalytic efficiency of proteasomal protein degradation in response to amino acid starvation, an adaptive response co-opted by cancer cells for asparaginase resistance.
  • ||||||||||  Review, Journal:  Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma. (Pubmed Central) -  Jul 20, 2022   
    Regardless of the approach to asparagine depletion, it has continually demonstrated to be among the most important components of ALL therapy. Despite regular use over the past 50 years, and its incorporation into the standard of care treatment for ALL, there remains much yet to be discovered and ample room for improvement within the utilization of asparaginase therapy.
  • ||||||||||  mercaptopurine / Generic mfg., doxorubicin hydrochloride / Generic mfg., vincristine / Generic mfg.
    SOD2 PROMOTES ACUTE LEUKEMIA ADAPTATION TO AMINO ACID STARVATION THROUGH THE N-DEGRON PATHWAY (Hall Lehar 3-4) -  May 13, 2022 - Abstract #EHA2022EHA_2604;    
    Conclusion The interaction of SOD2 and the N-degron pathway represents a previously unknown molecular adaptation of cancer cells in response to amino acid starvation. These results serve as a strong proponent for an in-depth characterization of the N-degron pathway in mediating leukemia cell fitness upon amino acid starvation and thus provide a basis for therapeutic intervention in refractory leukemias.
  • ||||||||||  Oncaspar liquid (pegaspargase) / Servier
    PEGASPARGASE LEVELS IN INFANTS WITH ALL: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP TRIAL AALL15P1 () -  Apr 20, 2022 - Abstract #ASPHO2022ASPHO_329;    
    Importantly, all reported levels were > 0.1 IU/mL, the commonly accepted minimum therapeutic level, and the vast majority were > 0.4 IU/mL, believed to be the optimal therapeutic level, suggesting that, despite a reduced BSA-based pegaspargase dose when compared to older children, infants achieve adequate asparagine depletion. No SAA levels were indicative of silent inactivation and there were no patients with pegaspargase hypersensitivity reported, highlighting that the asparaginase immune response relationship may differ in infants compared to older patients.
  • ||||||||||  Journal:  Biomimetic lipidic nanovectors for effective asparaginase supramolecule delivery. (Pubmed Central) -  Apr 8, 2022   
    Fluorescent probes and computational simulations were used to reveal possible interactions between serum albumin/trypsin and Aase/nanovector membrane components which were partly responsible for enhanced bioavailability and bioactivity of AS-XLNs compared to Aase. AS-XLNs significantly increased cytotoxicity against pulmonary tumor cells, due to synergistic effects of Aase and nanovector membrane components (killing tumor cells through apoptosis induced by asparagine depletion and autophagy inhibition or via targets such as vascular endothelial growth factor A, alpha-amylase, p-selectin or androgen receptor).
  • ||||||||||  Trial termination:  Trial of Oncaspar (clinicaltrials.gov) -  May 16, 2013   
    P1/2,  N=56, Terminated, 
    Not yet recruiting --> Recruiting Active, not recruiting --> Terminated