Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma

Miller, Todd W.; Traphagen, Nicole A.; Li, Jing; Lewis, Lionel D.; Lopes, Bruna Corrêa; Asthagiri, Ashok R.; Loomba, Johanna; Jong, Jenny De; Schiff, David; Patel, Sohil H.; Purow, Benjamin; Fadul, Camilo E.

doi:10.1007/s11060-019-03258-0

Cited by 35 publications

(42 citation statements)

References 43 publications

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“…The study of CDK4/6 inhibitors was mainly focused on oncology, including breast cancer, glioblastoma, and myeloma [25][26][27][28][29]. Many basic and clinical studies have confirmed the efficacy of CDK4/6 inhibitors on the treatment of various solid human cancers [25][26][27][28][29]. Nevertheless, publications in other areas, such as Nano-medicine research on CDK4/6 inhibitors, are still few and delayed [30,31].…”

Section: Discussionmentioning

confidence: 99%

“…Unlike other anti-tumor drugs, there have been many studies of the oncological mechanism and biological signaling pathways for CDK4/6 inhibitors, in line with the development trend of translational medicine [32]. With the increase in the number of clinical trials, studies on CDK4/6 inhibitors have also expanded from breast cancer to other types of human cancer [25][26][27][28][29]. However, in view of the adverse effects and drug resistance associated with CDK4/6 inhibitors, many drug candidates will be investigated; thus, dominant countries, such as the USA, Europe, and China, should strengthen their support to complete high-quality basic research and clinical trials of CDK4/6 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

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Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis

et al. 2021

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Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are frequently used anti-cancer agents in hormone receptor-positive breast cancers. This study assessed the course of research and development (R&D) for CDK4/6 inhibitors in terms of publications over the past two decades. Methods: The Web of Science (WOS) and PubMed databases were searched to identify publications related to research on CDK4/6 inhibitors since 2001. The VOS Viewer software was used to analyze co-occurring keywords to stratify the publication data and collaborations in research. Results: There were 1395 publications related to research on CDK4/6 inhibitors since 2001. Eight of the top 10 institutions originated from the USA and the other two were a Swiss Pharmaceutical Company and French Research Institute. Bardia A, the first author for some of the articles published in the USA, was the most prolific with 25 publications. The journal with the most publications was Cancer Res with 162 publications. Basic research comprised six of the 10 most frequently cited publications and the rest consisted of three reviews and a clinical trial. The most common keywords for publications since 2011 were "palbociclib", "abemaciclib", "ribociclib" and "double blind", indicating the successful development of CDK4/6 inhibitors as anticancer drugs. Conclusions: This study provides a comprehensive review of the CDK4/6 inhibitors R&D history. The data imply that drug development in this field is a decade-long process and clinical trials have been performed before clinical applications. Thereafter, research was conducted on the adverse effects and drug resistance associated with the inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis

et al. 2021

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“…Many clinical trials for different targeted therapies, including the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib ( 51 ), the D2 dopamine receptor (DRD2) inhibitor ONC201 ( 52 ), the tyrosine kinase receptor (TRK) inhibitor larotrectinib ( 53 ), the multitarget MET and VEGFR2 inhibitor cabozantinib ( 54 ) and the 26S proteasome and the NF-κB pathway inhibitor bortezomib ( 55 ), have been conducted. ONC201 and larotrectinib showed efficacy, and ONC201 had possible antitumor activity, especially for patients with H3.3 K27M mutation.…”

Section: Targeted Therapymentioning

confidence: 99%

Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Chen

Liu

et al. 2021

Chinese Journal of Cancer Research

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Recurrence is a major concern for adult patients with glioblastomas (GBMs), and the prognosis remains poor. Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM (rGBM). Here, we review the results of clinical trials for the systematic therapy of rGBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1 (PD-1) inhibitors are promising agents for rGBM, while regorafenib is effective in both O 6 -methylguanine DNA methyltransferase ( MGMT ) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase ( IDH ) mutations or second recurrence can benefit from vocimagene amiretrorepvec (Toca 511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.

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“…Just like palbociclib, ribociclib was effective in preclinical pediatric CNS tumors (DIPGx7 cortical allograft) [41]. However, ribociclib was ineffective in humans because of PI3K/mTOR pathway upregulation in recurrent tumors (phase 0/1b studies) [42,43].…”

Section: Cdk4/6 Inhibitorsmentioning

confidence: 99%

Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology?

Riess

Irmscher

Salewski

et al. 2020

Cancer Metastasis Rev

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Cyclin-dependent kinases (CDK) control the cell cycle and play a crucial role in oncogenesis. Pharmacologic inhibition of CDK has contributed to the recent clinical approval of dual CDK4/6 inhibitors for the treatment of breast and small cell lung cancer. While the anticancer cell effects of CDK inhibitors are well-established, preclinical and early clinical studies describe additional mechanisms of action such as chemo- and radiosensitization or immune stimulation. The latter offers great potential to incorporate CDK inhibitors in immune-based treatments. However, dosing schedules and accurate timing of each combination partner need to be respected to prevent immune escape and resistance. In this review, we provide a detailed summary of CDK inhibitors in the two solid cancer types head and neck cancer and glioblastoma multiforme; it describes the molecular mechanisms of response vs. resistance and covers strategies to avoid resistance by the combination of immunotherapy or targeted therapy.

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Tumor pharmacokinetics and pharmacodynamics of the CDK4/6 inhibitor ribociclib in patients with recurrent glioblastoma

Cited by 35 publications

References 43 publications

Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis

Global Trend in Research and Development of CDK4/6 Inhibitors for Clinical Cancer Therapy: A Bibliometric Analysis

Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology?

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