A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer

Bryan, Margarette; Pulte, E. Dianne; Toomey, K.; Pliner, Lillian; Pavlick, Anna C.; Saunders, Tracie; Wieder, Robert

doi:10.1007/s10637-010-9478-3

Cited by 63 publications

(52 citation statements)

References 16 publications

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“…The previously established LM38-LP cell line (passage [15][16][17][18][19][20][21][22][23][24][25], derived from a BALB/c murine mammary papillary adenocarcinoma with tumourigenic and metastatic capacities [8], was used throughout this study. This cell line is composed of two main subpopulations, antigenically characterized as luminal epithelial (LEP) and myoephitelial (MEP), which remain up to the 30th passage [12].…”

Section: Cell Culturesmentioning

confidence: 99%

“…Due to their role in growth regulation and differentiation, natural and synthetic retinoids are widely evaluated in clinical trials for cancer treatment and prevention [18][19][20]. Besides, since retinoic acid is known to act as a key regulator of embryonic stem cell behaviour, retinoids may not only induce apoptosis, but also differentiation of cancer stem cells.…”

Section: Introductionmentioning

confidence: 99%

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Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

et al. 2015

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Our results show that the luminal epithelial (LEP) and myoephitelial (MEP) mammary LM38-P subpopulations respond differently to ATRA, i.e., the LEP subpopulation responds with increased cell cycle arrest and apoptosis and the MEP subpopulation responds with increased senescence and adhesion, thereby decreasing its invasive capacity. Finally, we identified a third subpopulation with stem/progenitor cell characteristics within the LM38-LP mammary adenocarcinoma cell line, which appears to be non-responsive to ATRA.

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Section: Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

et al. 2015

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“…In a recent experimental approach, ATRA was able to eliminate breast cancer cells that gained CSC properties, suggesting its effectiveness in cancer resistant to conventional oncologic therapies [109]. However, ATRA has to date performed poorly in clinical trials; in a pilot phase II study 17 metastatic or recurrent breast cancer patients were treated with ATRA in combination with paclitaxel showing time to progression and survival rates similar to those reported for paclitaxel alone [110]. …”

Section: Therapeutic Consequencesmentioning

confidence: 99%

Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

Krawczyk

Meier-Stiegen

Banys

et al. 2014

BioMed Research International

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Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulation. During EMT epithelial antigens are downregulated; thus, such tumor cells might elude classical epithelial marker-based detection. Several researchers postulated that some CTCs express stem cell-like phenotype; this might lead to chemoresistance and enhanced metastatic potential of such cells. In the present review, we discuss current data on EMT and stem cell markers in CTCs of breast cancer and their clinical significance.

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“…38 Restoring RA levels to normal in order to drive differentiation and arrest proliferation is thus especially attractive for liver carcinomas. 39 Although a phase II clinical trial with free RA plus TAX did not report significant benefit over TAX alone against breast carcinoma, 40 nanoparticle formulations of RA plus TAX are understudied. RA plus TAX filomicelles (Figure 1A) are therefore assessed here with the various needed comparisons in vitro and in vivo with several solid tumor models.…”

Section: Introductionmentioning

confidence: 99%

Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival

et al. 2018

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Drug resistance and relapse is common in cancer treatments with chemotherapeutics, and while drug combinations with naturally occurring, differentiation-inducing retinoic acid (RA) provide remission-free cures for one type of liquid tumor, solid tumors present major problems for delivery. Here, inspired by filoviruses that can be microns in length, flexible filomicelles that self-assemble from an amphiphilic block copolymer (PEG−PCL) are shown to effectively deliver RA and paclitaxel (TAX) to several solid tumor models, particularly in the liver. These hydrophobic compounds synergistically load into the cores of the elongated micelles, and the coloaded micelles prove most effective at causing cell death, ploidy, and durable regression of tumors compared to free drugs or to separately loaded drugs. RA-TAX filomicelles also reduce mortality of human lung or liver derived cancers engrafted at liver, intraperitoneal, and subcutaneous sites in immunodeficient mice. In vitro studies show that the dual drug micelles effectively suppress proliferation while upregulating a generic differentiation marker. The results highlight the potency of dual-loaded filomicelles in killing cancer cells or else driving their differentiation away from growth.

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A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer

Abstract: The data suggest this is a well tolerated regimen with modest response rates but with time to progression and survival rates similar to those reported for paclitaxel alone and relatively high rates of stable disease in this sample of patients.

Cited by 63 publications

References 16 publications

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival

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