The dawn of targeted therapies for triple negative breast cancer (TNBC): a snapshot of investigational drugs in phase I and II trials

Huynh, My-my; Pambid, Mary Rose; Jayanthan, Aarthi; Dorr, Andrew; Los, Gerrit; Dunn, Sandra E.

doi:10.1080/13543784.2020.1818067

Cited by 18 publications

(19 citation statements)

References 63 publications

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“…Triple-negative breast cancer (TNBC) is clinically defined as a breast cancer subtype that lacks expression of the estrogen receptor (ER) and progesterone receptor (PR) and has no amplification of HER2 [ 16 , 17 ]. TNBC accounts for approximately 15–20% of diagnosed breast cancers [ 16 , 17 , 18 , 19 , 20 , 21 ]. However, few targeted therapies with limited clinical outcomes have been approved for TNBC treatment [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

You

Cho

et al. 2021

Pharmaceuticals

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Triple-negative breast cancer (TNBC) is a subset of breast cancer with aggressive characteristics and few therapeutic options. The lack of an appropriate therapeutic target is a challenging issue in treating TNBC. Although a high level expression of epidermal growth factor receptor (EGFR) has been associated with a poor prognosis among patients with TNBC, targeted anti-EGFR therapies have demonstrated limited efficacy for TNBC treatment in both clinical and preclinical settings. However, with the advantage of a number of clinically approved EGFR inhibitors (EGFRis), combination strategies have been explored as a promising approach to overcome the intrinsic resistance of TNBC to EGFRis. In this review, we analyzed the literature on the combination of EGFRis with other molecularly targeted therapeutics or conventional chemotherapeutics to understand the current knowledge and to provide potential therapeutic options for TNBC treatment.

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Section: Introductionmentioning

confidence: 99%

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

You

Cho

et al. 2021

Pharmaceuticals

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“…Triple-negative breast cancer (TNBC) is defined clinically as being negative for both the estrogen receptor (ER) and progesterone receptor (PR) and having no amplification of human epidermal growth factor receptor 2 (HER2) [ 1 , 2 ]. Therefore, the therapeutic options that feature drugs targeting these proteins are not available for TNBC patients.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the therapeutic options that feature drugs targeting these proteins are not available for TNBC patients. TNBC accounts for approximately 15–20% of breast cancers and is known as the most aggressive breast cancer [ 1 , 2 , 3 , 4 , 5 , 6 ]. Although TNBCs respond well to conventional adjuvant chemotherapies, including taxanes, anthracyclines, capecitabines, and/or platins, resistance to these agents and distant metastasis diminish overall prognosis [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Up to date, four targeted therapies have been approved by the US Food and Drug Administration (FDA). These therapies include the poly [adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) inhibitors, olaparib and talazoparib; the programmed cell death ligand 1 (PD-L) inhibitor, atezolizumab; and antibody drug conjugates (ADCs), sacituzumab govitecan [ 2 ]. However, most treatments exhibit limited durable clinical responses [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Combining existing therapeutics is a promising way to treat intractable cancers, such as pancreatic cancer or TNBC [ 2 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. For example, blocking the PI3K/AKT pathway [ 25 ], MET [ 30 ], or mammalian target of rapamycin complex 1 (mTORC1) [ 33 ] sensitized TNBC cells to EGFR inhibitors (EGFRis).…”

Section: Introductionmentioning

confidence: 99%

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Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells

You

Cho

et al. 2021

Cancers

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There is an unmet medical need for the development of new targeted therapeutic strategies for triple-negative breast cancer (TNBC). With drug combination screenings, we found that the triple combination of the protein kinase inhibitors (PKIs) of the epidermal growth factor receptor (EGFR), v-akt murine thymoma viral oncogene homolog (AKT), and MAPK/ERK kinase (MEK) is effective in inducing apoptosis in TNBC cells. A set of PKIs were first screened in combination with gefitinib in the TNBC cell line, MDA-MB-231. The AKT inhibitor, AT7867, was identified and further analyzed in two mesenchymal stem-like (MSL) subtype TNBC cells, MDA-MB-231 and HS578T. A combination of gefitinib and AT7867 reduced the proliferation and long-term survival of MSL TNBC cells. However, gefitinib and AT7867 induced the activation of the rat sarcoma (RAS)/ v-raf-1 murine leukemia viral oncogene homolog (RAF)/MEK/ extracellular signal-regulated kinase (ERK) pathway. To inhibit this pathway, MEK/ERK inhibitors were further screened in MDA-MB-231 cells in the presence of gefitinib and AT7867. As a result, we identified that the MEK inhibitor, PD-0325901, further enhanced the anti-proliferative and anti-clonogenic effects of gefitinib and AT7867 by inducing apoptosis. Our results suggest that the dual inhibition of the AKT and MEK pathways is a novel potential therapeutic strategy for targeting EGFR in TNBC cells.

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Radiation Therapy in Patients with Germline Mutations: a Review of the Current Evidence

DeFoe,

Balogun,

Sabih

et al. 2023

Curr Breast Cancer Rep

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The dawn of targeted therapies for triple negative breast cancer (TNBC): a snapshot of investigational drugs in phase I and II trials

Cited by 18 publications

References 63 publications

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells

Radiation Therapy in Patients with Germline Mutations: a Review of the Current Evidence

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