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Targeted Therapies in Breast Cancer

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Resistance to Targeted Therapies in Breast Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 16))

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Abstract

As the most prevalent form of cancer found in women, breast cancer is an active area of research and clinical study. Treatments for cancer patients have traditionally relied upon chemotherapy, but an increasing emphasis is placed on targeted therapies as a safer and more effective way to treat cancer. Therapies that target specific aspects of cancerous cells may be especially significant for triple negative breast cancer (TNBC), which is often associated with poor patient prognosis and currently lacks reliable targeted treatment options. Many therapies for breast cancer have been extensively studied and examined in clinical settings, while others show future potential and require further investigation. This chapter will focus on six targeted therapies, describing mechanisms of action and current methods of inhibition. Inducible nitric oxide synthase (iNOS) overexpression is correlated with increased cell proliferation and mammosphere production, while inhibition has been shown to minimize these effects in cancerous cells. The PI3K pathway is an essential component of intracellular signaling that is frequently dysregulated in tumors. Poly(ADP-ribose) polymerases (PARP) are implicated in DNA damage repair, and are the focus of numerous ongoing clinical trials. Protein tyrosine kinase 6 (PTK6) has been associated with cell proliferation and tumor growth in breast cancer cells, while the serine/threonine cyclin-dependent kinase (CDK) protein family is a crucial component of cell cycle regulation and an important area of research for targeted therapies. Finally, aberrant activation of the Wnt/β-catenin signaling pathway has been implicated in multiple breast cancer subtypes, particularly with respect to the prevalence β-catenin mutations in TNBC. These pathways represent promising topics in the field of targeted therapies, and with increased research may contribute to the development of superior and precise treatments for breast cancer.

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Abbreviations

ABC:

ATP-binding cassette

APC:

Adenomatous polyposis coli

CDK:

Cyclin-dependent kinase

CK1α:

Casein kinase-1α

CSC:

Cancer stem cell

DSB:

Double-stranded break

DVL:

Dishevelled

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

FAK:

Focal adhesion kinase

FOXM1:

Forkhead box M1

FZD:

Frizzled

GSK3β:

Glycogen synthase kinase 3β

HER2:

Human epidermal growth factor 2

HR:

Homologous recombination

HR+:

Hormone receptor-positive

iNOS:

Inducible nitric oxide synthase

NOS:

Nitric oxide synthase

NSAID:

Nonsteroidal anti-inflammatory drug

PARP:

Poly(ADP-Ribose) polymerase

PARPi:

PARP inhibitor

PI3K:

Phosphoinositide 3-kinase

Prcn:

Porcupine

PTEN:

Phosphatase and tensin homolog

PTK6:

Protein tyrosine kinase 6

Rb:

Retinoblastoma

RTK:

Receptor tyrosine kinase

SSD:

Single-stranded break

STAT:

Signal transducer and activator of transcription

TCF/LEF:

T-cell factor/lymphoid enhancer factor

TNBC:

Triple-negative breast cancer

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Acknowledgements

The authors thank Ms. Casey Stefanski for critical review of the document. Work in the Prosperi laboratory is supported by the Navari Family Foundation and the Indiana Clinical and Translational Sciences Institute, funded in part by grant #UL1 TR001108 (A. Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. The awards were made to JRP. ATL was supported by a COS-SURF fellowship through the University of Notre Dame.

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“No potential conflicts of interest were disclosed.”

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Authors and Affiliations

  1. College of Science, University of Notre Dame, Notre Dame, IN, USA

    Anna T. Lyons & Jenifer R. Prosperi

  2. Harper Cancer Research Institute, South Bend, IN, USA

    Jenifer R. Prosperi

  3. Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA

    Jenifer R. Prosperi

  4. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine – South Bend, South Bend, IN, USA

    Jenifer R. Prosperi

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  1. Anna T. Lyons
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Correspondence to Jenifer R. Prosperi .

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  1. Harper Cancer Research Institute, University of Notre Dame, South Bend, Indiana, USA

    Jenifer R. Prosperi

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Lyons, A.T., Prosperi, J.R. (2017). Targeted Therapies in Breast Cancer. In: Prosperi, J. (eds) Resistance to Targeted Therapies in Breast Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-70142-4_6

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