A randomized phase III study of napabucasin [BBI608] (NAPA) vs placebo (PBO) in patients (pts) with pretreated advanced colorectal cancer (ACRC): the CCTG/AGITG CO.23 trial

Jonker, Derek J.; Nott, Louise; Yoshino, Takayuki; Gill, Satinder; Shapiro, Jeremy; Ohtsu, Atsushi; Zalcberg, John; Vickers, Michael M.; Wei, Alice C.; Gao, Yuan; Tebbutt, Niall C.; Markman, Ben; Esaki, Taito; Koski, Sheryl; Hitron, Matthew; Magoski, Nadine M; Simes, John; Li, C.; Tu, Dongsheng; O’Callaghan, Chris

doi:10.1093/annonc/mdw370.03

Cited by 9 publications

(7 citation statements)

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“…Aberrant signaling pathways, including AKT/mTOR, Hedgehog, and Wnt, have been reported in CSCs and multi-targeting therapies have been proposed (54). The first-in-class cancer stemness inhibitor napabucasin (BBI 608), which targets signal transducer and activator of transcription 3 (Stat3), Nanog, and Wnt/β-catenin pathways, has been reported to improve OS in patients with positive phospho-STAT3 recurrent colorectal cancer (55,56). Itraconazole may be a promising agent for targeting CSCs in relapsed disease of multiple types of cancer; therefore, further preclinical studies on CSCs and the surrounding stroma cells are warranted.…”

Section: Future Perspectivesmentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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Abstract. Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/β-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

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Section: Future Perspectivesmentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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“…Both clinical trials showed a high disease control rate (DCR) including patients with partial response, stable disease or tumor regression, which confirms the safety of these combinations with encouraging anti-tumor activity [ 128 , 129 , 130 ]. Thereafter, a phase III study was designed to evaluate the efficacy and safety of BBI608 versus placebo with the best supportive care in patients with advanced CRC who had failed all available standard therapy (NCT01830621) [ 131 ]. In this trial, BBI608 did not improve overall survival (OS) or progression-free survival (PFS) in unselected patients with advanced CRC but did improve OS in pSTAT3-positive patients compared to the placebo group, suggesting that STAT3 may be an important target for CRC treatment [ 131 , 132 ].…”

Section: Clinical Trials On Colorectal Cancer Stem Cellsmentioning

confidence: 99%

The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials

Hervieu

Christou

Battu

et al. 2021

Cancers

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The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient’s overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity.

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“…Subgroup analyses are ongoing to detect a benefit for patients with high levels of cancer cells expressing STAT3 [100,101]. In patients with advanced colorectal cancer, napabucasin led to a survival benefit, only in patients with tumors expressing phospho-STAT3 [102].…”

Section: Targeting Stemness Pathways To Overcome Chemoresistancementioning

confidence: 99%

Targeting Cancer Stem Cells to Overcome Chemoresistance

Nunes

Hamdan

Lebœuf

et al. 2018

IJMS

124

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Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness pathways or cancer stem cell surface markers. Gold nanoparticles have emerged as innovative tools, particularly for photo-thermal therapy since they can be excited by laser to induce hyperthermia. Gold nanoparticles can be functionalized with antibodies to specifically target cancer stem cells. Preclinical studies using photo-thermal therapy have demonstrated the feasibility of targeting chemo-resistant cancer cells to reverse clinical chemoresistance. Here, we review the data linking cancer stem cells and chemoresistance and discuss the way to target them to reverse resistance. We particularly focus on the use of functionalized gold nanoparticles in the treatment of chemo-resistant metastatic cancers.

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A randomized phase III study of napabucasin [BBI608] (NAPA) vs placebo (PBO) in patients (pts) with pretreated advanced colorectal cancer (ACRC): the CCTG/AGITG CO.23 trial

Cited by 9 publications

References 0 publications

Repurposing itraconazole as an anticancer agent

Repurposing itraconazole as an anticancer agent

The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials

Targeting Cancer Stem Cells to Overcome Chemoresistance

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