Evidence map›Paper›PMID 39560206›Full record

ArticleCancer medicine2024

A Combinatorial Functional Precision Medicine Platform for Rapid Therapeutic Response Prediction in AML.

Noor Rashidha Binte Meera Sahib, Jameelah Sheik Mohamed, Masturah Bte Mohd Abdul Rashid, Jayalakshmi, Yihao Clement Lin, Yen Lin Chee, Bingwen Eugene Fan, Sanjay De Mel, Melissa Gaik Ming Ooi, Wei-Ying Jen and 1 more

Abstract read
In one paragraph

Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Noor Rashidha Binte Meera SahibCancer Science Institute of Singapore, National University of Singapore, Singapore.ORCID https://orcid.org/0009-0004-0305-8846
Jameelah Sheik MohamedNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Masturah Bte Mohd Abdul RashidKYAN Technologies Pte Ltd, Singapore.
JayalakshmiCancer Science Institute of Singapore, National University of Singapore, Singapore.
Yihao Clement LinDepartment of Haematology, Tan Tock Seng Hospital, Singapore.
Yen Lin CheeNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Bingwen Eugene FanDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Sanjay De MelNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Melissa Gaik Ming OoiNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wei-Ying JenNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.ORCID https://orcid.org/0000-0002-9339-3362
Edward Kai-Hua ChowCancer Science Institute of Singapore, National University of Singapore, Singapore.

Funding

Baillie Gifford Health Innovation FundCancer Science Institute of Singapore Research Centres of Excellence (RCE) Main Grant (NUS Strategic Fund)Singapore lYMPHoma translatiONal studY (SYMPHONY) OFLCG18May-0028
6 · The paper itself

Abstract

backgroundDespite advances made in targeted biomarker-based therapy for acute myeloid leukemia (AML) treatment, remission is often short and followed by relapse and acquired resistance. Functional precision medicine (FPM) efforts have been shown to improve therapy selection guidance by incorporating comprehensive biological data to tailor individual treatment. However, effectively managing complex biological data, while also ensuring rapid conversion of actionable insights into clinical utility remains challenging.

methodsWe have evaluated the clinical applicability of quadratic phenotypic optimization platform (QPOP), to predict clinical response to combination therapies in AML and reveal patient-centric insights into combination therapy sensitivities. In this prospective study, 51 primary samples from newly diagnosed (ND) or refractory/relapsed (R/R) AML patients were evaluated by QPOP following ex vivo drug testing.

resultsIndividualized drug sensitivity reports were generated in 55/63 (87.3%) patient samples with a median turnaround time of 5 (4-10) days from sample collection to report generation. To evaluate clinical feasibility, QPOP-predicted response was compared to clinical treatment outcomes and indicated concordant results with 83.3% sensitivity and 90.9% specificity and an overall 86.2% accuracy. Serial QPOP analysis in a FLT3-mutant patient sample indicated decreased FLT3 inhibitor (FLT3i) sensitivity, which is concordant with increasing FLT3 allelic burden and drug resistance development. Forkhead box M1 (FOXM1)-AKT signaling was subsequently identified to contribute to resistance to FLT3i.

conclusionOverall, this study demonstrates the feasibility of applying QPOP as a functional combinatorial precision medicine platform to predict therapeutic sensitivities in AML and provides the basis for prospective clinical trials evaluating ex vivo-guided combination therapy.

Indexed as

Leukemia, Myeloid, AcutePrecision MedicineAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorDrug Resistance, NeoplasmFemalefms-Like Tyrosine Kinase 3Forkhead Box Protein M1HumansMaleMiddle AgedMutationProspective StudiesBiomarkers, TumorFLT3 protein, humanfms-Like Tyrosine Kinase 3Forkhead Box Protein M1FOXM1 protein, humanAMLcombinatorial drug sensitivityFLT3functional precision medicine

Identifiers

PMID39560206
PMCPMC11574777

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.