NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Kumar, Shaji; Callander, Natalie S.; Hillengaß, Jens; Liedtke, Michaela; Baljevic, Muhamed; Campagnaro, Erica; Castillo, Jorge J.; Chandler, Jason C.; Cornell, Robert F.; Costello, Caitlin; Efebera, Yvonne A.; Faiman, Matthew; Garfall, Alfred L.; Godby, Kelly N.; Holmberg, Leona; Htut, Myo; Huff, Carol Ann; Kang, Yubin; Landgren, Ola; Malek, Ehsan; Martin, Thomas G.; Omel, James; Raje, Noopur; Sborov, Douglas W.; Singhal, Seema; Stockerl-Goldstein, Keith; Tan, Carlyn; Weber, Donna M.; Johnson-Chilla, Alyse; Keller, Jennifer; Kumar, Rashmi

doi:10.6004/jnccn.2019.0049

Cited by 139 publications

(124 citation statements)

References 51 publications

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“…467 In regard to relapsed MM, recommended therapies usually involve PIs and immunomodulatory drugs (IMiDs; e.g., lenalidomide, pomalidomide) in doublet or triplet combinations with corticosteroids or other systemic therapies including the anti-CD38 monoclonal antibody daratumumab and the immunoglobulin G1 (IgG1) monoclonal antibody isatuximab for the CD38 receptor. [468][469][470] For patients with MCL and diffuse large B-cell lymphoma, combination treatment of PIs and chemotherapies or histone deacetylase inhibitors also yields benefits, 471,472 which may also overcome the impact of gain-of-function p53 mutations in solid tumors. 473 In the clinic, with regard to bortezomibresistant tumors, the combination treatments of bortezomib with chemotherapy drugs such as doxorubicin, plerixafor and daratumumab have shown improved clinical outcomes, suggesting that conventional chemotherapy could increase the sensitivity of bortezomib to malignancies.…”

Section: Targeting E3 Enzymesmentioning

confidence: 99%

The role of ubiquitination in tumorigenesis and targeted drug discovery

Deng

Meng

Chen

et al. 2020

Sig Transduct Target Ther

464

308

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Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" and "quality" of various proteins, serving to ensure cell homeostasis and guarantee life activities. The regulation of ubiquitination is multifaceted and works not only at the transcriptional and posttranslational levels (phosphorylation, acetylation, methylation, etc.) but also at the protein level (activators or repressors). When regulatory mechanisms are aberrant, the altered biological processes may subsequently induce serious human diseases, especially various types of cancer. In tumorigenesis, the altered biological processes involve tumor metabolism, the immunological tumor microenvironment (TME), cancer stem cell (CSC) stemness and so on. With regard to tumor metabolism, the ubiquitination of some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc and P53 significantly regulates the activity of the mTORC1, AMPK and PTEN-AKT signaling pathways. In addition, ubiquitination in the TLR, RLR and STING-dependent signaling pathways also modulates the TME. Moreover, the ubiquitination of core stem cell regulator triplets (Nanog, Oct4 and Sox2) and members of the Wnt and Hippo-YAP signaling pathways participates in the maintenance of CSC stemness. Based on the altered components, including the proteasome, E3 ligases, E1, E2 and deubiquitinases (DUBs), many molecular targeted drugs have been developed to combat cancer. Among them, small molecule inhibitors targeting the proteasome, such as bortezomib, carfilzomib, oprozomib and ixazomib, have achieved tangible success. In addition, MLN7243 and MLN4924 (targeting the E1 enzyme), Leucettamol A and CC0651 (targeting the E2 enzyme), nutlin and MI-219 (targeting the E3 enzyme), and compounds G5 and F6 (targeting DUB activity) have also shown potential in preclinical cancer treatment. In this review, we summarize the latest progress in understanding the substrates for ubiquitination and their special functions in tumor metabolism regulation, TME modulation and CSC stemness maintenance. Moreover, potential therapeutic targets for cancer are reviewed, as are the therapeutic effects of targeted drugs.Signal Transduction and Targeted Therapy (2020) 5:11; https://doi.

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Section: Targeting E3 Enzymesmentioning

confidence: 99%

The role of ubiquitination in tumorigenesis and targeted drug discovery

Deng

Meng

Chen

et al. 2020

Sig Transduct Target Ther

464

308

View full text Add to dashboard Cite

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“…37 At present, maintenance therapy post-ASCT is widely recommended, whereas consolidation is not as routinely supported. 2,22,[38][39][40][41] Nevertheless, given the heterogeneity of MM, bortezomib-based consolidation therapy may have a role to play in combination with maintenance treatment in specific patient subgroups or treatment settings. Prolonged followup of current studies is warranted.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials

Straka

Knop

Vogel

et al. 2019

European J of Haematology

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Objective: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). Methods:Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m 2 IV on days 1, 8,15,22) or observation only.

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“…Eligible patients met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for MM. [12] The inclusion criteria were as follows: 1) aged from 18-70 years; 2) diagnosis of MM in accordance with established diagnostic criteria; and 3) patients had to undergo our standard scanning protocol with WB-DWI and 18 F-FDG PET/CT. We excluded patients with bone diseases other than MM, and MM patients without bone lesions.…”

Section: Subjectsmentioning

confidence: 99%

Diagnostic Value of WB-DWI Versus 18 F-FDG PET/CT for the Detection of Multiple Myeloma

Zhang¹,

Zhang²,

Bian³

et al. 2020

Preprint

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BACKGROUND Whole body diffusion weighted imaging (WB-DWI) is commonly used for the detection of multiple myeloma (MM). Comparative data on the efficiency of WB-DWI compared with 18 F positron emission tomography computed tomography ( 18 F-FDG PET/CT) to detect MM are lacking. METHODS This was a retrospective, single-center study of twenty-two patients with MM enrolled from January 2019 to December 2019. All patients underwent WB-DWI and 18 F-FDG PET/CT. Pathological and clinical manifestations as well as radiologic follow-up were used for diagnosis. The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of both methods were compared. The appearance diffusion coefficient (ADC) values of MM lesions and false-positive lesions were estimated. RESULTS A total of 214 MM bone lesions were evaluated. WB-DWI showed a higher overall accuracy than PET/CT (75.7% and 55.6%, respectively; < 0.05). However, for sensitivity, specificity, positive predictive value and negative predictive value, there were no significant differences for WB-DWI vs PET/CT (99.3% and 83.9%, 64.9% and 94.8%, 63.6% and 54.2%, 98.1% and 65.3%, respectively). The ADC value for MM lesions was significantly lower than that for false-positive lesions (p < 0.001). Receiver operating curve (ROC) curve analysis showed that the AUC was 0.846, and when the cut-off value was 0.745×10 -3 mm 2 /s, the sensitivity and specificity were 86.0% and 82.4%, respectively, which distinguished MM lesions from non-MM lesions. CONCLUSION WB-DWI may be a useful tool for the diagnosis of MM bone disease due to to higher overall accuracy and measurements of ADC values compared with PET/CT.

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NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

Cited by 139 publications

References 51 publications

The role of ubiquitination in tumorigenesis and targeted drug discovery

The role of ubiquitination in tumorigenesis and targeted drug discovery

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials

Diagnostic Value of WB-DWI Versus 18 F-FDG PET/CT for the Detection of Multiple Myeloma

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