Phase Ib study of recombinant human (rh)Apo2L/TRAIL in combination with paclitaxel, carboplatin, and bevacizumab (PCB) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

Soria, Jean‐Charles; Smit, Egbert F.; Khayat, David; Besse, Benjamin; Burton, J. D.; Yang, Xiaolu; Hsu, Meier; Braun, A.; Reese, David; Blackhall, F.

doi:10.1200/jco.2008.26.15_suppl.3539

Cited by 9 publications

(4 citation statements)

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“…This double-pronged approach utilizes independent mechanisms to eliminate tumor cells directly as well as inhibiting factors that stimulate bone resorption. Both rhApo2L/TRAIL (dulanermin) and the anti-human RANKL antibody denosumab are showing promise in the clinic in the treatment of solid tumors 21,22 and bone metastasis (including breast and prostate cancer), 49,50 respectively. Our findings provide the rationale and highlight the potential for future consideration of rhApo2L/TRAIL in combination with RANKL inhibition for the treatment of skeletal tumors.…”

Section: Discussionmentioning

confidence: 99%

“…20 Early clinical trial data suggest that rhApo2L/TRAIL is generally safe and well tolerated and also provide preliminary evidence of antitumor activity. 21,22 In this study, we evaluated whether the effects of RANKL inhibition coupled with the pro-apoptotic receptor agonist rhApo2L/TRAIL could prevent breast cancer-induced bone destruction and reduce skeletal tumor burden in a murine model of bone metastases. Combining a RANKL inhibitor (RANK-Fc) with rhApo2L/TRAIL was superior to rhApo2L/TRAIL alone at reducing skeletal tumor burden in the bone metastasis model.…”

Section: Mda-mb-231-bb-luc Tumor Cells Are Sensitive To Rhapo2l/ Traimentioning

confidence: 99%

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Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis

Holland

Miller²,

Jones³

et al. 2010

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Section: Mda-mb-231-bb-luc Tumor Cells Are Sensitive To Rhapo2l/ Traimentioning

confidence: 99%

Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis

Holland

Miller²,

Jones³

et al. 2010

Cancer Biology & Therapy

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“…There are a number of TRAIL or TRAIL receptor-based clinical trials for cancer patients (Table 1). One such agent, recombinant human TRAIL (rhTRAIL), dulanermin, functions as a ligand to death receptors DR4 and DR5 [70]. In a clinical report, a patient with refractory chondrosarcoma who developed progressive metastatic chondrosarcoma to the lung showed a partial response to dulanermin treatment that was potentially mediated by DR4 present in the patient tumor cells [71].…”

Section: Targeting the Core Machinery Of The Trail Pathwaymentioning

confidence: 99%

Developing TRAIL/TRAIL death receptor-based cancer therapies

Yuan

Gajan

Chu

et al. 2018

Cancer Metastasis Rev

183

144

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate the apoptosis pathway by binding to its associated death receptors DR4 and DR5. The activation of the TRAIL pathway in inducing tumor-selective apoptosis leads to the development of TRAIL-based cancer therapies, which include recombinant forms of TRAIL, TRAIL receptor agonists, and other therapeutic agents. Importantly, TRAIL, DR4, and DR5 can all be induced by synthetic and natural agents that activate the TRAIL apoptosis pathway in cancer cells. Thus, understanding the regulation of the TRAIL apoptosis pathway can aid in the development of TRAIL-based therapies for the treatment of human cancer.

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“…However, the low number of subjects may render the results inconclusive. In another phase IB trial of rhTRAIL in combination with paclitaxel, carboplatin and bevacizumab in patients with advanced non-small cell lung cancer (NSCLC), the overall response rate reported was 56% (53).…”

Section: The Apoptosis Signaling Pathways As Anti-tumor Targetsmentioning

confidence: 99%

Programmed Cell Death Pathways and Current Antitumor Targets

et al. 2009

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Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.

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Phase Ib study of recombinant human (rh)Apo2L/TRAIL in combination with paclitaxel, carboplatin, and bevacizumab (PCB) in patients (pts) with advanced non-small cell lung cancer (NSCLC)

Cited by 9 publications

References 0 publications

Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis

Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis

Developing TRAIL/TRAIL death receptor-based cancer therapies

Programmed Cell Death Pathways and Current Antitumor Targets

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