A refractory case of CDK4-amplified spinal astrocytoma achieving complete response upon treatment with a Palbociclib-based regimen:a case report

Lin, Jietao; Yu, Liguo; Fu, Yuanfeng; Chen, Hanrui; Zheng, Xiongwei; Wang, Shutang; Gao, Chan; Cao, Yang; Lin, Lizhu

doi:10.1186/s12885-020-07061-3

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…The use of cell cycle or apoptosis pathways as targets stems from the use of these pathways in the treatment of other tumors, in particular. In the present study, only four clinical studies included cell cycle/apoptosis pathway inhibitors, namely the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib, the mouse double minute 2 (MDM2) inhibitor idasanutlin, the ribonucleotide reductase inhibitor Motexafin Gadolinium, and the 26S proteasome inhibitor bortezomib [ 36 , 57 , 58 , 59 ]. CDK and MDM2 inhibitors were also prevalent in laboratory studies testing existing therapies [ 150 , 156 , 160 , 161 , 165 , 176 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies

Muzyka,

Goff,

Choudhary

et al. 2023

IJMS

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Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy—namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories—clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets—and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.

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Section: Discussionmentioning

confidence: 99%

Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies

Muzyka,

Goff,

Choudhary

et al. 2023

IJMS

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“…The patient underwent two surgeries and received radiation therapy, TMZ, and bevacizumab, but nonetheless progressed. Treatment with Palbociclib, a selective CKD4 inhibitor, was effective at promoting tumor regression, and the patient was alive at the 2-year follow-up visit, illustrating the potential of personalized therapy for patients with intramedullary tumors ( 80 ).…”

Section: Molecular Landscapementioning

confidence: 96%

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

2022

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Intramedullary astrocytomas represent approximately 30%–40% of all intramedullary tumors and are the most common intramedullary tumor in children. Surgical resection is considered the mainstay of treatment in symptomatic patients with neurological deficits. Gross total resection (GTR) can be difficult to achieve as astrocytomas frequently present as diffuse lesions that infiltrate the cord. Therefore, GTR carries a substantial risk of new post-operative deficits. Consequently, subtotal resection and biopsy are often the only surgical options attempted. A midline or paramedian sulcal myelotomy is frequently used for surgical resection, although a dorsal root entry zone myelotomy can be used for lateral tumors. Intra-operative neuromonitoring using D-wave integrity, somatosensory, and motor evoked potentials is critical to facilitating a safe resection. Adjuvant radiation and chemotherapy, such as temozolomide, are often administered for high-grade recurrent or progressive lesions; however, consensus is lacking on their efficacy. Biopsied tumors can be analyzed for molecular markers that inform clinicians about the tumor’s prognosis and response to conventional as well as targeted therapeutic treatments. Stratification of intramedullary tumors is increasingly based on molecular features and mutational status. The landscape of genetic and epigenetic mutations in intramedullary astrocytomas is not equivalent to their intracranial counterparts, with important difference in frequency and type of mutations. Therefore, dedicated attention is needed to cohorts of patients with intramedullary tumors. Targeted therapeutic agents can be designed and administered to patients based on their mutational status, which may be used in coordination with traditional surgical resection to improve overall survival and functional status.

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Antineoplastics

2021

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A refractory case of CDK4-amplified spinal astrocytoma achieving complete response upon treatment with a Palbociclib-based regimen:a case report

Cited by 4 publications

References 18 publications

Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies

Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

Antineoplastics

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