Inflammatory breast cancer (IBC): clues for targeted therapies

Fernandez, Sandra V.; Robertson, Fredika M.; Pei, Jianming; Aburto-Chumpitaz, Lucy; Mu, Zhaomei; Chu, Khoi; Alpaugh, R. Katherine; Huang, Yong; Cao, Yu; Ye, Zaiming; Cai, Kathy Q.; Boley, Kimberly M.; Klein‐Szanto, Andres J.; Devarajan, Karthik; Addya, Sankar; Cristofanilli, Massimo

doi:10.1007/s10549-013-2600-4

Cited by 71 publications

(83 citation statements)

References 35 publications

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“…Furthermore, other studies have unequivocally demonstrated the presence of E-cadherin in a percentage of both primary breast tumors and distant metastases (48) and a correlation between cellular aggregation and successful metastasis was first published over 50 years ago (49,50). More recent studies examining circulating tumor cells (CTCs) have provided evidence that these cells often exist in the bloodstream as multicellular aggregates (29,51,52). Our data may help explain the significance of these findings in that aggregation may occur in CTCs and may facilitate metastasis through the inhibition of anoikis.…”

Section: Discussionmentioning

confidence: 99%

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Rayavarapu

Heiden²,

Pagani³

et al. 2015

Journal of Biological Chemistry

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Background: Cancer cells evade death caused by extracellular matrix (ECM)-detachment to facilitate metastasis. Results: ErbB2-expressing cancer cells form aggregates during ECM-detachment that promote survival signaling through EGFR. Conclusion: Multicellular aggregation in ErbB2 positive cancer cells promotes survival by preventing EGFR degradation. Significance: Disrupting aggregation or inhibiting EGFR may be effective strategies to eliminate ErbB2-expressing cancer cells during ECM-detachment.

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Section: Discussionmentioning

confidence: 99%

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Rayavarapu

Heiden²,

Pagani³

et al. 2015

Journal of Biological Chemistry

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“…The biology of breast cancer is complex, involving oncogenesis, evasion of host immune defense mechanisms, angiogenesis, invasion and metastasis . Recently, the contribution of interleukins, pleiotropic cytokines, to cancer progression has been demonstrated (Fernandez et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effect of NUCKS-1 Overexpression on Cytokine Profiling in Obese Women with Breast Cancer

Soliman

Zineldeen²,

El-Khadrawy³

2014

Asian Pacific Journal of Cancer Prevention

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Background: Overweight and obesity are recognized as major drivers of cancers including breast cancer. Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers, including breast cancer. Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. Materials and Methods: This study included 39 females with breast cancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profiles were determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures werealso recorded for all participants. Results: IL-6, IL-12 and LCN2 were significantly higher in control obese and breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression was significantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positively correlated with obesity markers in all obese patients. Conclusions: Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management.

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“…Collectively, the pathological and molecular underpinnings of the disease contribute to the poor prognosis of IBC patients relative to other, more common subtypes of human breast cancer (8). Therefore IBC is unequivocally considered a formidable clinical challenge in contemporary cancer medicine (2)(3)(4)(5)(6)(7)(8). Within this clinical context, the emerging field of "theranostic" (a combination of the terms "therapeutic" and "diagnostic") approaches offers an attractive avenue for the concurrent detection and treatment of cancer.…”

mentioning

confidence: 99%

Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes

Dobroff

D’Angelo

Eckhardt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.inflammatory breast cancer | ligand-directed theranostics | molecular imaging | gene therapy | AAVP B reast cancer remains a major cause of cancer death in women (1), and one of its most lethal presentations is inflammatory breast carcinoma (IBC), a clinicopathological diagnosis characterized by diffuse erythema/edema involving the skin of the breast (a sign classically known as "peau d'orange") caused by tumor emboli within the dermal lymphatics. Although IBC comprises <5% of breast cancer cases, the tumor accounts for more than 10% of breast cancer mortality in the United States (2, 3). IBC is considered aggressive because it evolves rapidly-over days to weeks rather than months-with most patients presenting with lymph node involvement and more than 30% of patients having distant metastases at diagnosis (4, 5). Although IBC, like non-IBC breast cancers, is a heterogeneous disease and can occur as any of the five molecular subtypes, the IBC is most commonly ErbB2 overexpressing or triple negative (6), thus rendering a large armamentarium of targeted drugs ineffective. Finally, IBC generally presents with high-grade histology, elevated cell proliferation rate, and angiolymphatic invasion (5, 7). Indeed, the hallmark lymphatic invasion dictates the requirement for initial systemic treatment of IBC, because micrometastatic disease likely has occurred even in the Significance Inflammatory breast cancer (IBC) is defined clinically and pathologically. Dermal lymphatic invasion is typical but is neither necessary nor sufficient for diagnosis; sentinel lymph node biopsy is contraindicated, challenging multidisciplinar...

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Inflammatory breast cancer (IBC): clues for targeted therapies

Cited by 71 publications

References 35 publications

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Effect of NUCKS-1 Overexpression on Cytokine Profiling in Obese Women with Breast Cancer

Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes

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