Phase II open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma

Leng, Yun; Qiu, Lugui; Hou, Jian; Zhao, Yaozhong; Zhang, Xuejun; Yang, Shiming; Xi, Hao; Huang, Zhongxia; Pan, Ling; Chen, Wen-Ming

doi:10.1186/s40880-016-0140-0

Cited by 18 publications

(13 citation statements)

References 18 publications

(16 reference statements)

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“…CPT (circularly permuted TRAIL) is a recombinant human mutant of Apo2L/TRAIL developed by Beijing Sunbio Biotech, Co. Ltd. in China, and was tested in relapsed and refractory multiple myeloma as a single agent [115,116], or in combination with thalidomide (T), or in combination with thalidomide and dexamethasone (TD) [117,118]. Median PFS was 6.7 months in the CPT + TD group compared with 3.1 months for the TD group [118].…”

Section: Extrinsic Pathway Targetingmentioning

confidence: 99%

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

Greer

Lipkowitz

Takebe

2019

Cancers

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: Evasion from apoptosis is an important hallmark of cancer cells. Alterations of apoptosis pathways are especially critical as they confer resistance to conventional anti-cancer therapeutics, e.g., chemotherapy, radiotherapy, and targeted therapeutics. Thus, successful induction of apoptosis using novel therapeutics may be a key strategy for preventing recurrence and metastasis. Inhibitors of anti-apoptotic molecules and enhancers of pro-apoptotic molecules are being actively developed for hematologic malignancies and solid tumors in particular over the last decade. However, due to the complicated apoptosis process caused by a multifaceted connection with cross-talk pathways, protein–protein interaction, and diverse resistance mechanisms, drug development within the category has been extremely challenging. Careful design and development of clinical trials incorporating predictive biomarkers along with novel apoptosis-inducing agents based on rational combination strategies are needed to ensure the successful development of these molecules. Here, we review the landscape of currently available direct apoptosis-targeting agents in clinical development for cancer treatment and update the related biomarker advancement to detect and validate the efficacy of apoptosis-targeted therapies, along with strategies to combine them with other agents.

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Section: Extrinsic Pathway Targetingmentioning

confidence: 99%

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

Greer

Lipkowitz

Takebe

2019

Cancers

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“…It accounts for 5–10% of all plasma cell neoplasms and comprises two subsets, including solitary extramedullary plasmacytoma (EMP) and solitary plasmacytoma of bone (SBP). EMP accounts for 3 to 5% of all plasma cell neoplasms, a percentage that is less than that reported for SBP [ 1 – 3 ]. EMP may originate in soft tissues throughout the body, although it most frequently occurs in the upper respiratory tract and oral cavity.…”

Section: Introductionmentioning

confidence: 89%

The role of initial 18F-FDG PET/CT in the management of patients with suspected extramedullary plasmocytoma

Zhang

et al. 2018

Cancer Imaging

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BackgroundExtramedullary plasmacytoma (EMP) is a plasma cell malignancy that originates in soft tissues without evidence of systemic spread, and its management differs from other plasma cell neoplasms. The purpose of the present study was to evaluate the role of initial 18F-FDG PET/CT in the management of patients with clinical suspected EMP.Methods18F-FDG PET/CT scans performed in 21 patients (M/F = 12/9, mean age 51.1 ± 15.3 years) with clear suspicion of EMP from 2006 to 2015 were analysed retrospectively. The detection of new lesions and the change in treatment were evaluated.ResultsPET/CT detected new lesions in 38.1% (8/21) of patients with 17 lesions, and lymph nodes were the most common site, accounting for 70.6% (12/17) of all lesions, followed by bone (n = 2), and less frequently, breast (n = 1), lung (n = 1), and stomach (n = 1). These findings resulted in treatment changes in 7 patients with EMP. Among these, 4 patients had major treatment changes and 3 patients had minor changes. Of the 21 patients, progression to MM was observed in 8 patients (8/21, 38.1%). In univariate analysis, tumour size > 4 cm and partial response (PR) after treatment were significant prognostic factors for Progression-free survival (PFS).ConclusionsOur data indicated that 18F-FDG PET/CT is helpful in the detection of additional lesions throughout the body, including lymph node involvement and distant additional lesion, which may have resulted in treatment change.

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“…The monotherapy was well tolerated with 20–30% partially- or better-responding patients. No DLT and MTD could be observed [127]. A further dose-finding phase II study enrolled thalidomide-resistant relapsed refractory multiple myeloma (RRMM) patients and investigated the combination of CPT with the MM-approved drug thalidomide.…”

Section: On the Trail For Targeted Cancer Therapymentioning

confidence: 99%

TRAILblazing Strategies for Cancer Treatment

Kretz

Trauzold

Hillenbrand

et al. 2019

Cancers

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In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities. Thus, several so-called TRAIL receptor agonists (TRAs) were developed. Unfortunately, clinical testing of these TRAs did not reveal any significant anticancer activity, presumably due to inherent or acquired TRAIL resistance of most primary tumour cells. Since the potential power of TRAIL-based therapies still lies in TRAIL’s explicit cancer cell-selectivity, a desirable approach going forward for TRAIL-based cancer therapy is the identification of substances that sensitise tumour cells for TRAIL-induced apoptosis while sparing normal cells. Numerous of such TRAIL-sensitising strategies have been identified within the last decades. However, many of these approaches have not been verified in animal models, and therefore potential toxicity of these approaches has not been taken into consideration. Here, we critically summarise and discuss the status quo of TRAIL signalling in cancer cells and strategies to force tumour cells into undergoing apoptosis triggered by TRAIL as a cancer therapeutic approach. Moreover, we provide an overview and outlook on innovative and promising future TRAIL-based therapeutic strategies.

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Phase II open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma

Cited by 18 publications

References 18 publications

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox

The role of initial 18F-FDG PET/CT in the management of patients with suspected extramedullary plasmocytoma

TRAILblazing Strategies for Cancer Treatment

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