New and Emerging Targeted Therapies for Advanced Breast Cancer

Lau, Kristie H.; Tan, Alexandra M.; Shi, Yihui

doi:10.3390/ijms23042288

Cited by 67 publications

(33 citation statements)

References 78 publications

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“…In this context, a broad range of both natural as well as synthetic compounds, including HDIs, have been identified and have become an interesting class of active agents in the therapy of TNBC. HDIs, including SIRTi are promising anti-cancer drugs due to their ability to induce apoptosis or inhibit proliferation and cell cycle in numerous cancer cells [ 2 , 27 , 28 ], including BC [ 29 ]. Although in clinical trials, HDIs did not demonstrate spectacular therapeutic effects in BC treatment as single agents, it has been shown that HDIs increase the sensitivity of BC cells to radio- and chemotherapy [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Breast cancer (BC) is the most common malignancy in females worldwide [ 1 ]. Based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or human epidermal growth factor receptor 2 (HER2), four main subtypes of BC were distinguished, including luminal A, luminal B, HER2 positive (HER2+) and basal-like or triple-negative breast cancer (TNBC) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Endocrine therapy has been shown to be effective in hormone receptor-positive BCs and is a common choice for adjuvant therapy. Yet, due to the aggressive nature of TNBC as well as lack of estrogen, progesterone and HER2 receptors, endocrine and targeted therapies are ineffective in the treatment of TNBC patients [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Wawruszak

Łuszczki

Okon

et al. 2022

IJMS

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Breast cancer (BC) is a heterogeneous disease with different intrinsic subtypes. The most aggressive subtype of BC–triple-negative breast cancer (TNBC) is characterized by high heterogeneity and metastasis rate, poor prognosis and lack of therapeutic targets due to the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Targeted therapies have been approved for many other cancers and even other subtypes of BC, but treatment options for TNBC are still mainly limited to chemotherapy. Therefore, new, more effective treatment regimens are needed. Combined chemotherapy with two or more active agents is considered a promising anti-neoplasm tool in order to achieve better therapeutic response and reduce therapy-related adverse effects. The study demonstrated an antagonistic effect commonly used in TNBC therapy cytostatic drug-paclitaxel (PAX) and sirtuin inhibitor: cambinol (CAM) in BT-549, MDA-MB-468 and HCC1937 TNBC cell lines. The type of pharmacological interaction was determined by a precise and rigorous pharmacodynamic method-isobolographic analysis. The cytotoxic and anti-proliferative effects of CAM used alone or combined with PAX were determined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU) assays, respectively. Induction of apoptosis in TNBC cell lines after PAX and CAM treatment applied individually or in combination was determined by flow cytometry (FACS) as a number of cells with active caspase-3. It has been observed that both agents used separately inhibit cell proliferation and induce apoptosis; however, applying them in combination ameliorated antiproliferative and pro-apoptotic effects in all analyzed TNBC cell lines. Our results demonstrate that CAM and PAX used in combination act antagonistically, limiting anti-cancer efficacy and showing the importance of preclinical testing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Wawruszak

Łuszczki

Okon

et al. 2022

IJMS

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“…Despite the more accurate methods of treatment and diagnosis being developed, the incidence and death rate of breast cancer continues to rise [1][2][3][4]. Due to the drug resistance mechanism and the high heterogeneity of breast cancers, additional targets are needed to be explored and highly specific drugs are continuously in need of investigation [2,[4][5][6][7]. The development of more effective targeted therapeutic approaches could serve as a new paradigm for breast cancer treatment in the personalized medicine era.…”

Section: Introductionmentioning

confidence: 99%

“…Breast cancer cells display distinct patterns such as excessive production of certain distinctive proteins on the cell surface [6,7]. Human epidermal growth factor receptor (HER2) or ERBBR2 is one of the most common cell-surface targets for treating breast cancer [7].…”

Section: Introductionmentioning

confidence: 99%

Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R

Ayudhya¹,

Graidist²,

Tipmanee³

2022

Molecules

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Breast cancer cell proliferation and migration are inhibited by naturally extracted trans-(−)-kusunokinin. However, three additional enantiomers of kusunokinin have yet to be investigated: trans-(+)-kusunokinin, cis-(−)-isomer and cis-(+)-isomer. According to the results of molecular docking studies of kusunokinin isomers on 60 breast cancer-related proteins, trans-(−)-kusunokinin was the most preferable and active component of the trans-racemic mixture. Trans-(−)-kusunokinin targeted proteins involved in cell growth and proliferation, whereas the cis-(+)-isomer targeted proteins involved in metastasis. Trans-(−)-kusunokinin targeted CSF1R specifically, whereas trans-(+)-kusunokinin and both cis-isomers may have bound AKR1B1. Interestingly, the compound’s stereoisomeric effect may influence protein selectivity. CSF1R preferred trans-(−)-kusunokinin over trans-(+)-kusunokinin because the binding pocket required a ligand planar arrangement to form a π-π interaction with a selective Trp550. Because of its large binding pocket, EGFR exhibited no stereoselectivity. MD simulation revealed that trans-(−)-kusunokinin, trans-(+)-kusunokinin and pexidartinib bound CSF1R differently. Pexidartinib had the highest binding affinity, followed by trans-(−)-kusunokinin and trans-(+)-kusunokinin, respectively. The trans-(−)-kusunokinin-CSF1R complex was found to be stable, whereas trans-(+)-kusunokinin was not. Trans-(±)-kusunokinin, a potential racemic compound, could be developed as a selective CSF1R inhibitor when combined.

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Current scenario of chalcone hybrids with antibreast cancer therapeutic applications

Wang,

Zhu,

Zhang

et al. 2024

Archiv der Pharmazie

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Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%–80% of breast cancer with early‐stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure–activity relationships as well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

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New and Emerging Targeted Therapies for Advanced Breast Cancer

Cited by 67 publications

References 78 publications

Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis

Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications

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