<i>FLT3</i> Mutation Testing in Acute Myeloid Leukemia

Gupta, Arjun; Viswanatha, David S.; Patnaik, Mrinal M.

doi:10.1001/jamaoncol.2017.0257

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Since then, several methods have been developed or adapted for identifying mutations and aberrant karyotypes (Table 1) [ [45][46][47][48][49][50][51]. These methods vary in their sensitivity, turnaround time, and development stage [52]. Some methods have been used in the clinic for >10 years, while others are still being validated.…”

Section: Methods For Testing Flt3mentioning

confidence: 99%

The importance ofFLT3mutational analysis in acute myeloid leukemia

Patnaik

2017

Leukemia & Lymphoma

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Activating mutations in FMS-like tyrosine kinase 3 (FLT3), including internal tandem duplications (ITDs) and tyrosine kinase domain (TKD) mutations, are common in patients with acute myeloid leukemia (AML). FLT3-ITD is a negative prognostic factor that remains prognostically relevant even after intensive chemotherapy and/or stem cell transplant. FLT3 testing was historically viewed as being purely prognostic; however, with the advent of FLT3 inhibitors, it will likely be seen as both prognostic and predictive. The multikinase inhibitor midostaurin, in combination with chemotherapy, is the first targeted agent to significantly prolong survival in patients with newly diagnosed FLT3-mutated AML and was recently approved by health authorities. Recently, the European LeukemiaNet recommended FLT3 testing (both TKD and ITD) for all patients with AML, with results required within 3 days. The need for optimized, multigene platform testing incorporating FLT3 mutations will increase as knowledge of interactions between FLT3 and other myeloid-relevant mutations grows.

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Section: Methods For Testing Flt3mentioning

confidence: 99%

The importance ofFLT3mutational analysis in acute myeloid leukemia

Patnaik

2017

Leukemia & Lymphoma

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“…With only 10% of leukemia patients and 25% of AML patients presenting with mutations in FLT3, biomarkers are becoming increasingly useful to connect patients to the correct therapy [ 32 ]. As one example, the companion diagnostic LeukoStrat CDx FLT3 mutation assay, was FDA-approved alongside midostaurin in April 2017, and the Phase III trial showed an improved OS rate of 23% [ 33 ].…”

Section: Classic Biomarker-based Approaches For Precision Diagnosticsmentioning

confidence: 99%

Cancer Immunotherapy and Personalized Medicine: Emerging Technologies and Biomarker Based Approaches

Maciejko¹,

Smalley²,

Goldman³

2017

J Mol Biomark Diagn

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Purpose of review The vision and strategy for the 21st century treatment of cancer calls for a personalized approach in which therapy selection is designed for each individual patient. While genomics has led the field of personalized cancer medicine over the past several decades by connecting patient-specific DNA mutations with kinase-targeted drugs, the recent discovery that tumors evade immune surveillance has created unique challenges to personalize cancer immunotherapy. In this mini-review we will discuss how personalized medicine has evolved recently to accommodate the emerging era of cancer immunotherapy. Moreover, we will discuss novel platform technologies that have been engineered to address some of the persisting limitations. Recent finding Beginning with early evidence in personalized medicine, we discuss how biomarker-driven approaches to predict clinical success have evolved to account for the heterogeneous tumor ecosystem. In the emerging field of cancer immunotherapy, this challenge requires the use of a novel set of tools, distinct from the classic approach of next-generation genomic sequencing-based strategies. We will introduce new techniques that seek to tailor immunotherapy by re-programming patient-autologous T-cells, and new technologies that are emerging to predict clinical efficacy by mapping infiltration of lymphocytes, and harnessing fully humanized platforms that reconstruct and interrogate immune checkpoint blockade, ex-vivo. Summary While cancer immunotherapy is now leading to durable outcomes in difficult-to-treat cancers, success is highly variable. Developing novel approaches to study cancer immunotherapy, personalize treatment to each patient, and achieve greater outcomes is penultimate to developing sustainable cures in the future. Numerous techniques are now emerging to help guide treatment decisions, which go beyond simple biomarker-driven strategies, and are now we are seeking to interrogate the entirety of the dynamic tumor ecosystem.

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Preclinical characterization of CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3 for gastric, bladder, and squamous cell lung cancer

Popiel,

Stańczak,

Skupińska

et al. 2024

Front. Oncol.

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Fibroblast Growth Factor Receptors (FGFRs) are a family of receptor tyrosine kinases expressed on a plethora of cell membranes. They play crucial roles in both embryonic development and adult tissue functions. There is an increasing amount of evidence that FGFR-mediated oncogenesis is mainly related to gene amplification, activating mutations, or translocation in tumors of various histological types. Dysregulation of FGFRs has been implicated in a wide variety of neoplasms, such as bladder, gastric, and lung cancers. Given their functional significance, FGFRs emerge as promising targets for cancer therapy. Here, we introduce CPL304100, an innovative and highly potent FGFR1–3 kinase inhibitor demonstrating excellent in vitro biological activity. Comprehensive analyses encompassed kinase assays, cell line evaluations, PK/PD studies surface plasmon resonance studies, molecular docking, and in vivo testing in mouse xenografts. CPL304110 exhibited a distinctive binding profile to FGFR1/2/3 kinase domains, accompanied by a good safety profile and favorable ADMET parameters. Selective inhibition of tumor cell lines featuring active FGFR signaling was observed, distinguishing it from cell lines lacking FGFR aberrations (FGFR1, 2, and 3). CPL304110 demonstrated efficacy in both FGFR-dependent cell lines and patient-derived tumor xenograft (PDTX) in vivo models. Comparative analyses with FDA-approved FGFR inhibitors, erdafitinib and pemigatinib, revealed certain advantages of CPL304110 in both in vitro and in vivo assessments. Encouraging preclinical results led the way for the initiation of a Phase I clinical trial (01FGFR2018; NCT04149691) to further evaluate CPL304110 as a novel anticancer therapy.

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FLT3 Mutation Testing in Acute Myeloid Leukemia

Cited by 3 publications

References 9 publications

The importance ofFLT3mutational analysis in acute myeloid leukemia

The importance ofFLT3mutational analysis in acute myeloid leukemia

Cancer Immunotherapy and Personalized Medicine: Emerging Technologies and Biomarker Based Approaches

Preclinical characterization of CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3 for gastric, bladder, and squamous cell lung cancer

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