A Phase I Study of Pevonedistat Plus Capecitabine Plus Oxaliplatin in Patients With Advanced Gastric Cancer Refractory to Platinum (NCCH-1811)

Shoji, Hirokazu; Takahari, Daisuke; Nagashima, Kengo; Adachi, Jun; Boku, Narikazu

doi:10.2144/fsoa-2021-0023

Cited by 9 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…Approved by FDA for the treatment of leukemia in 2020, research studying the effect of Pevonedistat on solid tumors was in rapid growth, although no proven result has been announced. [43][44][45] Altogether, this study has shown the critical role of TME features in the prognosis of glioma and further constructed a novel signature based on immune-related genes. Clinicians and patients might benefit from TPS due to its high prediction accuracy.…”

Section: Tme Background and Tumor Mutation Status In Tps Risk Subgroupsmentioning

confidence: 92%

See 1 more Smart Citation

Development of a tumor microenvironment‐related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs

Zhang

et al. 2023

J Biochem & Molecular Tox

View full text Add to dashboard Cite

The involvement of the tumor microenvironment (TME) in the biology of gliomas has expanded, while it is yet uncertain its potential of supporting diagnosis and therapy choices. According to immunological characteristics and overall survival, cohorts of glioma patients from public databases were separated into two TME‐relevant clusters in this analysis. Based on differentially expressed genes between TME clusters and correlative regression analysis, a 21‐gene molecular classifier of TME‐related prognostic signature (TPS) was constructed. Afterward, the prognostic efficacy and effectiveness of TPS were assessed in the training and validation groups. The outcome demonstrated that TPS might be utilized alone or in conjunction with other clinical criteria to act as a superior prognostic predictor for glioma. Also, high‐risk glioma patients classified by TPS were considered to associate with enhanced immune infiltration, greater tumor mutation, and worse general prognosis. Finally, possible treatment medicines specialized for different risk subgroups of TPS were evaluated in drug databases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Tme Background and Tumor Mutation Status In Tps Risk Subgroupsmentioning

confidence: 92%

Development of a tumor microenvironment‐related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs

Zhang

et al. 2023

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…MLN4924 has shown anticancer effects in preclinical adult and pediatric tumor models 17,[51][52][53][54] and good tolerability in Phase I clinical trials as monotherapy and in combination studies in adult cancer patients 40,[55][56][57][58]. Two Phase I studies are ongoing using this agent in combinatorial approaches also in the pediatric cancer setting involving patients with leukemia/lymphoma (NCT03349281, NCT03813147).…”

Section: Discussionmentioning

confidence: 99%

A MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting

Pomella

Cassandri

Cossetti³

et al. 2022

Preprint

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is a pediatric mesenchymal-derived malignancy encompassing Fusion Positive (FP)-RMS expressing PAX3/7-FOXO1 and Fusion Negative (FN)-RMS often mutated in the RAS pathway. RMS expresses the master myogenic transcription factor MYOD that, paradoxically, in the tumor context is essential for tumor cell growth and survival. We identify here SKP2, an oncogenic E3-ubiquitin ligase of the SCF/CRL1 complex, as a critical driver of tumorigenesis downstream of MYOD in FN-RMS. SKP2 is overexpressed in RMS at the highest levels among several adult and pediatric cancers and its expression is maintained by MYOD through an intronic enhancer within the gene, in loop with its promoter. Mechanistically, in FN-RMS cells SKP2 functions by directly targeting p27Kip1 and p57Kip2 promoting their degradation. SKP2 knockdown causes cell cycle arrest by enhancing p27Kip1 and promotes differentiation by increasing p57Kip2, which in turn stabilizes MYOD. This leads to MYOD and MYOG increase and unlocks a myogenic program resulting in de novo expression of terminal muscle differentiation markers and cell fusion. SKP2 depletion strongly affects stemness and anchorage-independence features and prevents tumor growth. The investigational NEDDylation inhibitor MLN4924 (Pevonedistat) hampers SKP2 functions restraining FN-RMS cell survival and tumor growth. Our results uncover a MYOD-SKP2 axis crucial for the crosstalk between transcriptional and post-translational mechanisms that contribute to FN-RMS tumorigenesis and broaden the understanding of MYOD function. Furthermore, they suggest inhibition of NEDDylation as a potential therapeutic approach in this tumor.

show abstract

“…In a previous a study on CRC tissues, it was found that MLN4924 combined with oxaliplatin increased oxaliplatin-induced apoptosis ( 131 ). Although it has not yet entered clinical trials for CRC, phase I trials have been carried out in the therapeutic management of gastric carcinoma ( 155 ). CRC cells have also developed some drug resistance to platinum agents, such as the inhibition of drug accumulation in tumor cells, as well as the acquisition of EMT.…”

Section: Exploration Of Neddylation As a Potential Molecularly Target...mentioning

confidence: 99%

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

Wang,

Li,

et al. 2024

Int J Oncol

View full text Add to dashboard Cite

Neddylation, akin to ubiquitination, represents a post-translational modification of proteins wherein neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8-mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti-CRC target.

show abstract

A Phase I Study of Pevonedistat Plus Capecitabine Plus Oxaliplatin in Patients With Advanced Gastric Cancer Refractory to Platinum (NCCH-1811)

Cited by 9 publications

References 27 publications

Development of a tumor microenvironment‐related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs

Development of a tumor microenvironment‐related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs

A MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

Contact Info

Product

Resources

About