Updates to the drug‐resistant mechanism of proteasome inhibitors in multiple myeloma

Bai, Yang; Su, Xing

doi:10.1111/ajco.13459

Cited by 16 publications

(12 citation statements)

References 66 publications

(82 reference statements)

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“…Unfortunately, despite the initial promising effects and high efficacy of the proteasome inhibitors in MM treatment, in many patients, resistance has developed. Moreover, some patients do not respond to this treatment, or the side effects of the drugs are too severe [44][45][46][47].…”

Section: Resultsmentioning

confidence: 99%

Nostocyclopeptides as New Inhibitors of 20S Proteasome

et al. 2021

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Nostocyclopeptides (Ncps) are a small class of bioactive nonribosomal peptides produced solely by cyanobacteria of the genus Nostoc. In the current work, six Ncps were isolated from Nostoc edaphicum strain CCNP1411. The bioactivity of these compounds was tested in vitro against 20S proteasome, a proteolytic complex that plays an important role in maintaining cellular proteostasis. Dysfunction of the complex leads to many pathological disorders. The assays indicated selective activity of specific Ncp variants. For two linear peptide aldehydes, Ncp-A2-L and Ncp-E2-L, the inhibitory effects on chymotrypsin-like activity were revealed, while the cyclic variant, Ncp-A2, inactivated the trypsin-like site of this enzymatic complex. The aldehyde group was confirmed to be an important element of the chymotrypsin-like activity inhibitors. The nostocyclopeptides, as novel inhibitors of 20S proteasome, increased the number of natural products that can be considered potential regulators of cellular processes.

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Section: Resultsmentioning

confidence: 99%

Nostocyclopeptides as New Inhibitors of 20S Proteasome

et al. 2021

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“…Another therapeutic combination studied in the context of MM was the treatment of RV and bortezomib, the first-generation PI that induces cell-cycle arrest and apoptosis in myeloma cells [44,98]. In this study, the anti-MM effect resulted in an accumulation of viral and ubiquitinated proteins, which led to increased ER stress, NOXA induction and apoptosis.…”

Section: Oncolytic Viruses In Combination With Anti-mm Drugsmentioning

confidence: 90%

Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

Marchica

Costa

Donofrío

et al. 2021

IJMS

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Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.

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“…The underlying mechanisms are not yet evident in LCDD. But referring to the studies in MM, the potential mechanisms have been suggested as follows: proteasome mutations, such as proteasome β5 subunit (PSMB5); key stress signal pathway cross-talk, such as HSP family members; and bone marrow microenvironment changes, such as overexpression of IGF-1 (17). Interestingly, in light-chain amyloidosis, another aberrant light-chain gammopathy, the presence of t (11;14) is a marker of poor response to a bortezomib-based regimen (18,19).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review

Zhang

Zhou

et al. 2021

Front. Med.

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Background: Light-chain deposition disease (LCDD) is a rare systemic disorder characterized by the deposition of monoclonal light chains in organs. The kidney is a prominent target of light-chain deposition, with a median time to end-stage renal disease (ESRD) of 2.7 years and 5-year ESRD-free survival of 37%. The therapeutic management of LCDD remains ill-defined. In addition to bortezomib-based therapy as first-line therapy, the effect of lenalidomide on LCDD is rarely reported.Case Presentation: This study describes two male LCDD patients in their 60s with nephrotic syndrome and moderately impaired renal function. One patient had monoclonal IgGλ with underlying MGRS, and another had monoclonal IgGκ with underlying monoclonal gammopathy that developed into symptomatic MM during follow-up. The hallmarks of this disease were consistent with previous reports. Both patients initially received BCD therapy, but no hematological response was observed. Consequently, the nephrotic syndrome was refractory. Sequential Rd therapy was initiated, and partial hematological response and nephrotic remission were observed in the IgGλ patient but absent in the IgGκ patient.Conclusion: Limited reports have demonstrated the effect of lenalidomide in LCDD. We report the outcome of lenalidomide in two cases of bortezomib-resistant LCDD. This treatment might be a beneficial supplement for those unresponsive or intolerant to bortezomib in LCDD, but the effect should be prospectively investigated.

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Updates to the drug‐resistant mechanism of proteasome inhibitors in multiple myeloma

Cited by 16 publications

References 66 publications

Nostocyclopeptides as New Inhibitors of 20S Proteasome

Nostocyclopeptides as New Inhibitors of 20S Proteasome

Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review

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