A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma

Mercurio, Annalisa; Adriani, Giulia; Catalano, Alessia; Carocci, Alessia; Rao, Luigia; Lentini, Giovanni; Cavalluzzi, Maria Maddalena; Franchini, Carlo; Vacca, Angelo; Corbo, Filomena

doi:10.2174/0929867324666170601074646

Cited by 70 publications

(67 citation statements)

References 64 publications

(71 reference statements)

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“…It is not clear if the dose range and side-effect profile of TLD is ideal for Parkinson's disease, but newer compounds acting at TNF-α may already be optimized for rapid translation. [20][21][22] In conclusion, the present work strongly supports the growing hypothesis that indeed neuroinflammation is fanning the flames of LID. By providing targets and identifying compounds for further investigation, we may uncover new therapeutic avenues, not only to slow the progression of Parkinson's disease, but also to delay the emergence of one of the most deleterious side effects of its gold standard treatment.…”

supporting

confidence: 85%

“…From a repurposing perspective, TLD and its derivatives have seen a resurgence in medicine, in large part because of the very immunomodulatory and antiangiogenic features that were investigated here. 19,20 This would suggest there is a path forward for such compounds. It is not clear if the dose range and side-effect profile of TLD is ideal for Parkinson's disease, but newer compounds acting at TNF-α may already be optimized for rapid translation.…”

mentioning

confidence: 99%

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Neuroinflammation: Fanning the fire of l‐dopa‐induced dyskinesia

Bishop

2019

Movement Disorders

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supporting

confidence: 85%

mentioning

confidence: 99%

Neuroinflammation: Fanning the fire of l‐dopa‐induced dyskinesia

Bishop

2019

Movement Disorders

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“…Thalidomide's antiangiogenic effect via VEGF inhibition may play an important role in these HV patients whose lymph nodes are highly vascularized. 23 The TCP regimen was also effective in iMCD patients with PC and mixed histopathology, possibly related to plasma cell targeting with thalidomide and T-cell targeting with cyclophosphamide.…”

Section: Discussionmentioning

confidence: 96%

Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease

Zhang¹,

Zhao²,

Duan³

et al. 2019

Blood

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K E Y P O I N T S l The TCP regimen showed promising efficacy and safety to treat newly diagnosed iMCD.l Although more research is needed, the TCP regimen is an important treatment option, particularly when siltuximab is not available.Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti-interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m 2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P < .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105

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“…Thalidomide, a first generation immunomodulatory drug (IMiD), has a direct tumoricidal activity, an antiangiogenic effect and modulates TNF-α signaling through direct and/or indirect effects on the tumor microenvironment [15,[163][164][165][166][167], reduces FGF-2, VEGF, and IL-6 secretion in BM stromal cells and by MM cells [163]. It also interferes with NF-κB activity by blocking its ability to bind to DNA abrogating inflammatory/angiogenic cytokine production [165,166], and disrupts the direct interactions between MM plasma cells and BM stromal cells by modulation of cell surface adhesion molecules [167].…”

Section: Immunomodulators (Imids)mentioning

confidence: 99%

Angiogenesis and Antiangiogenesis in Multiple Myeloma

Ria¹,

Solimando²,

Melaccio³

et al. 2019

Update on Multiple Myeloma

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Multiple myeloma progression is characterized by a dense interaction between cancer cells and bone marrow microenvironment. The interactions of myeloma cells with various stromal cells and extracellular matrix components are the main regulator of the biological processes that underlie the progression of the disease and of the classic symptomatology correlated. The bone marrow of myeloma patients has recognized autocrine and paracrine loops that regulate multiple signaling pathways and the malignant phenotype of plasma cells. One of the pivotal biological processes which are responsible for myeloma progression is the formation of new vessels from existing ones, known as angiogenesis. It represents a constant hallmark of disease progression and a characteristic feature of the active phase of the disease. Near angiogenesis, other two ancestral processes were active in the bone marrow: vasculogenesis and vasculogenic mimicry. These processes are mediated by the angiogenic cytokines, interleukins, and inflammatory cytokines directly secreted by plasma cells and stromal cells. Neovascularization is also mediated by direct interaction between plasma cells and the various components of bone marrow microenvironment. The observation of the increased bone marrow angiogenesis in multiple myeloma and its correlation with disease activity and overall survival led to consider angiogenesis as a new target in the treatment of multiple myeloma.

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A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma

Cited by 70 publications

References 64 publications

Neuroinflammation: Fanning the fire of l‐dopa‐induced dyskinesia

Neuroinflammation: Fanning the fire of l‐dopa‐induced dyskinesia

Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease

Angiogenesis and Antiangiogenesis in Multiple Myeloma

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