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Arsenic combined to treat leukemia over 90% effective
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Arsenic combined to treat leukemia over 90% effective.
Arsenic is a “classic poison” with a long history; but if used correctly, it can also be an anti-cancer “good medicine”.
Acute promyelocytic leukemia was once one of the most dangerous and deadly leukemias. Chinese experts have innovatively combined arsenic (arsenic trioxide ATO, or “arsenic”) with all-trans retinoic acid (ATRA) to make the cure rate of acute promyelocytic leukemia positive for the PML-RARA fusion gene reach more than 90%.
In 2015, the ATO+ATRA program was also approved by the US FDA as the first-line treatment for promyelocytic leukemia.
However, 10% of patients still have a poor prognosis. Which patients are effective?
Not long ago, at the 62nd American Society of Hematology (ASH) Virtual Annual Meeting , Cellworks Group, a strategic partner of Good Medical Friends and a leading American oncology precision medicine company, announced the results of the myCare-021-01 clinical trial:
TRI predicts the response of PML-RARA fusion-positive acute promyelocytic leukemia (APL) patients to the combination therapy of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) with an accuracy rate of 93%.
The study also shows that TRI can accurately identify new drug resistance mechanisms in patients with acute promyelocytic leukemia, and propose alternatives for non-responders through patient-specific biomarkers.
TRI: Accurately predict the effectiveness of Anti-cancer
The vast majority (99%) of patients with acute promyelocytic leukemia carry the PML-RARA fusion gene, which is the most critical pathogenesis of acute promyelocytic leukemia.
PML-RARA fusion type promyelocytic leukemia has selective sensitivity to the targeted drugs ATO+ATRA, and the response rate exceeds 90%.
However, there are still a small number of patients with acute promyelocytic leukemia that do not respond, and the mechanism of drug resistance remains unclear.
The study used TRI to predict the response of PML-RARA fusion patients to ATO+ATRA combination therapy and determine the resistance mechanism.
“TRI can accurately predict the response of PML-RARA patients with acute promyelocytic leukemia to ATO+ATRA, avoid ineffective treatments and unnecessary side effects, and reduce treatment costs.”
Dr. Scott Howard, a professor at the University of Tennessee Health Science Center, said:
“In addition, we need to understand the drug resistance mechanism of non-responding patients with acute promyelocytic leukemia, so as to formulate more effective treatments and improve patient prognosis. In this study, TRI clarified the effects of patients who did not respond to ATO+ATRA. Clinically relevant genes are missing, and alternative treatments are given. By using this personalized approach to treat cancer patients, we are expected to achieve a 100% response rate.”
About myCare-021-01 clinical research
In this study, the results of 30 acute promyelocytic leukemia patients treated with ATRA or ATRA+ATO were compared with the results predicted by TRI.
The study used data from six publications, including: Whole Exome Sequencing (WES), Next Generation Genome Sequencing (NGS), Copy Number Variation (CNV) and/or Karyotype (Karyotype) data. The available genomic data for each atlas is input into TRI, and researchers use PubMed and other online academic resources to generate patient-specific disease models.
TRI uses patient-specific disease models for biological simulations, analyzes the influence of multi-omics variation information on the upstream and downstream of tumor cell signaling pathways, and calculates specific drugs or drug combinations to predict treatment effects.
The researchers performed ATO+ATRA protocol biological simulation on all 30 patients. The effect of treatment is evaluated by quantitatively measuring the effect of drugs on the cell growth score.
The cell growth score is a combination of quantitative values of cell proliferation, survival, and apoptosis, as well as a simulated impact on each patient’s specific disease biomarker score.
The models for each specific patient were also digitally screened to determine the response to ATO+ATRA.
The results of the study showed that in 30 cases, TRI correctly predicted the response to ATO+ATRA in 28 cases. The overall prediction accuracy rate is 93%, the prediction probability is 100%, the prediction net present value is 60%, the sensitivity is 93%, and the specificity is 100%.
Of the 30 patients who did not respond to ATO+ATRA, 2 patients found clinically relevant deletions in the EZH2, KMT2E and HIPK2 genes. These three genes are all located on chromosome 7, and these non-responders are accompanied by chromosome 7 monomer abnormalities.
TRI “sand table deduction”, let tumor treatment “knowledge”
Tumor Therapy Response Index (TRI) relies on computer biological simulation and machine learning artificial intelligence technology, breakthrough use of patient’s entire exome information to establish personalized disease models, conduct biological simulations, and analyze genome, proteome, transcriptome and epigenome mutations The influence of information on the upstream and downstream of tumor cell signaling pathways is calculated for specific drugs or drug combinations.
This is equivalent to a rigorous “sand table deduction” before treatment, so as to predict the best personalized medication plan for patients, and at the same time provide decision support based on molecular and genetic-level pathogenesis for clinicians who are faced with treatment options.
For more than a year, TRI testing has tailored matching precise treatment plans for hundreds of patients with difficult tumors in nearly one hundred tertiary hospitals across the country.
Arsenic combined to treat leukemia over 90% effective.
(source:internet, reference only)