Unveiling the antibody–drug conjugates portfolio in battling Triple-negative breast cancer: Therapeutic trends and Future horizon

Khadela, Avinash; Soni, Shruti; Shah, Aayushi; Pandya, Aanshi J.; Megha, Kaivalya; Kothari, Nirjari; CB, None Avinash

doi:10.1007/s12032-022-01884-9

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…ADCs are typically composed of a mAb covalently attached to a cytotoxic drug (payload) with the support of a stable chemical linker. 179 , 180 Trastuzumab deruxtecan is an ADC that targets HER2 and is conjugated with a topoisomerase I inhibitor, extecan derivative (Dxd). 181 Destiny-Breast04 was a phase III trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy.…”

Section: Future Directionsmentioning

confidence: 99%

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Jaradat,

Ayoub,

Al Sharie

et al. 2024

Technol Cancer Res Treat

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Triple-negative breast cancer (TNBC) comprises a group of aggressive and heterogeneous breast carcinoma. Chemotherapy is the mainstay for the treatment of triple-negative tumors. Nevertheless, the success of chemotherapeutic treatments is limited by their toxicity and development of acquired resistance leading to therapeutic failure and tumor relapse. Hence, there is an urgent need to explore novel targeted therapies for TNBC. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that are key regulators of intracellular signaling pathways controlling cell proliferation, differentiation, survival, and motility. Aberrant activity and/or expression of several types of RTKs have been strongly connected to tumorigenesis. RTKs are frequently overexpressed and/or deregulated in triple-negative breast tumors and are further associated with tumor progression and reduced survival in patients. Therefore, targeting RTKs could be an appealing therapeutic strategy for the treatment of TNBC. This review summarizes the current evidence regarding the antitumor activity of RTK inhibitors in preclinical models of TNBC. The review also provides insights into the clinical trials evaluating the use of RTK inhibitors for the treatment of patients with TNBC.

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Section: Future Directionsmentioning

confidence: 99%

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Jaradat,

Ayoub,

Al Sharie

et al. 2024

Technol Cancer Res Treat

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“…Other developments lie in more refined methods of treating HER2-positive and HER2-low tumors, using bispecific antibodies or antibody–drug conjugates (ADCs) that deliver a chemotherapy payload, such as trastuzumab deruxtecan (T-Dxd) [ 133 – 135 ]. ADCs also hold promise for TNBC [ 136 ]. For example, the trophoblast cell surface antigen 2 (TOP2)-directed ADCs Sacituzumab govitecan (SG) and Datopotamab deruxtecan (Dato-DXd) have shown strong and durable responses in patients with metastatic TNBC, resulting in regulatory approval of SG [ 137 ].…”

Section: Five Breakthroughs Of the Past Decadementioning

confidence: 99%

Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research

Amerongen

Bentires‐Alj

Boxtel

et al. 2023

J Mammary Gland Biol Neoplasia

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On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam, the Netherlands. Here, we embraced the opportunity to look back to identify the most prominent breakthroughs of the past ten years and to reflect on the main challenges that lie ahead for our field in the years to come. The outcomes of these discussions are presented in this position paper, in the hope that it will serve as a summary of the current state of affairs in mammary gland biology and breast cancer research for early career researchers and other newcomers in the field, and as inspiration for scientists and clinicians to move the field forward.

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“…Due to this aggressive clinical course and the lack of targeted treatment options, TNBC has a higher risk of death within 5 years of the initial diagnosis compared to other breast cancer subtypes [ 2 ]. Two recent additions to the TNBC therapeutic armamentarium, the immunotherapy pembrolizumab (Keytruda, Merck & Co Inc., Rahway, NJ, USA) and the antibody (Ab)–drug conjugate sacituzumab govitecan-hziy (Trodelvy, Gilead, Foster City, CA, USA), offer new hope for patients; however, response rates and duration are quite limited [ 4 , 5 ]. Thus, novel treatment options are urgently needed to improve patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

A Novel Class of Human ADAM8 Inhibitory Antibodies for Treatment of Triple-Negative Breast Cancer

Mineva,

Pianetti,

Das

et al. 2024

Pharmaceutics

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New targeted treatments are urgently needed to improve triple-negative breast cancer (TNBC) patient survival. Previously, we identified the cell surface protein A Disintegrin And Metalloprotease 8 (ADAM8) as a driver of TNBC tumor growth and spread via its metalloproteinase and disintegrin (MP and DI) domains. In proof-of-concept studies, we demonstrated that a monoclonal antibody (mAb) that simultaneously inhibits both domains represents a promising therapeutic approach. Here, we screened a hybridoma library using a multistep selection strategy, including flow cytometry for Ab binding to native conformation protein and in vitro cell-based functional assays to isolate a novel panel of highly specific human ADAM8 dual MP and DI inhibitory mAbs, called ADPs. The screening of four top candidates for in vivo anti-cancer activity in an orthotopic MDA-MB-231 TNBC model of ADAM8-driven primary growth identified two lead mAbs, ADP2 and ADP13. Flow cytometry, hydrogen/deuterium exchange–mass spectrometry (HDX-MS) and alanine (ALA) scanning mutagenesis revealed that dual MP and DI inhibition was mediated via binding to the DI. Further testing in mice showed ADP2 and ADP13 reduce aggressive TNBC characteristics, including locoregional regrowth and metastasis, and improve survival, demonstrating strong therapeutic potential. The continued development of these mAbs into an ADAM8-targeted therapy could revolutionize TNBC treatment.

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Unveiling the antibody–drug conjugates portfolio in battling Triple-negative breast cancer: Therapeutic trends and Future horizon

Cited by 10 publications

References 46 publications

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research

A Novel Class of Human ADAM8 Inhibitory Antibodies for Treatment of Triple-Negative Breast Cancer

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