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Exploring the therapeutic potential of ADC combination for triple-negative breast cancer

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Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Currently, standard treatment options for TNBC are limited to surgery, adjuvant chemotherapy, and radiotherapy. However, these treatment methods are associated with a higher risk of intrinsic or acquired recurrence. Antibody–drug conjugates (ADCs) have emerged as a useful and promising class of cancer therapeutics. ADCs, also known as “biochemical missiles”, use a monoclonal antibody (mAb) to target tumor antigens and deliver a cytotoxic drug payload. Currently, several ADCs clinical studies are underway worldwide, including sacituzumab govitecan (SG), which was recently approved by the FDA for the treatment of TNBC. However, due to the fact that only a small portion of TNBC patients respond to ADC therapy and often develop resistance, growing evidence supports the use of ADCs in combination with other treatment strategies to treat TNBC. In this review, we described the current utilization of ADCs and discussed the prospects of ADC combination therapy for TNBC.

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Abbreviations

TNBC:

Triple-negative breast cancer

ADCs:

Antibody–drug conjugates

mAb:

Monoclonal antibody

SG:

Sacituzumab govitecan

TDM1:

Trastuzumab emtansine

AML:

Acute myeloid leukemia

DAR:

Drug-to-antibody ratio

mTNBC:

Metastatic triple-negative breast cancer

Trop-2:

Anti-trophoblast cell-surface antigen 2

SGN-LIV1A:

Ladiratuzumab vedotin

MMAE:

Monomethyl auristatin E

EMT:

Epidermal-to-mesenchymal transition

ORR:

Objective response rate

DCR:

Disease control rate

DXd:

DX-8951 derivative

CPT:

Camptothecin

GGFG:

Glycine-phenylalanine-glycine

ILD:

Interstitial lung disease

TPC:

The physician’s choice

HR:

Hormone receptor

GV:

Glembatumumab vedotin

gpNMB:

Glycoprotein non-metastatic B

CBR:

Clinical benefit rate

CTCAE:

Common toxicity criteria for adverse events

DOR:

Duration of response

TILs:

Tumor infiltrating lymphocytes

pCR:

Pathological complete response

DFS:

Disease-free survival

BCS:

Breast conserving surgery rate

QOL:

Quality of life

TTP:

Time to progression

iDFS:

Invasive disease-free survival

DMFS:

Distant metastasis-free survival

BORR:

Best overall response rate

TOP1CCs:

TOP1 cleavage complexes

DLT:

Dose limiting toxicity

TTR:

Time-to-tumor response

rPFS:

Radiographic progression-free survival

MTIs:

Microtubule inhibitors

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Funding

This research was supported by the Natural Science Foundation of Jiangsu Province (Grant numbers BK20210096), National Natural Science Foundation of China (Grant numbers 82100109 and 82303622), Soochow University College Students Innovation and Entrepreneurship Fund (Grant numbers 5731514922).

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  1. Linlin Lu, Zihe Niu and Zhujun Chao contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China

    Kai Chen & Yaqin Shi

  2. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Linlin Lu

  3. Department of Soochow University School of Medicine, Soochow University Suzhou, Suzhou, 215000, China

    Zihe Niu & Zhujun Chao

  4. Department of Respiratory, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China

    Cuiping Fu

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Contributions

All authors contributed to the conception of the study and the preparation and approval of the paper. LL took the lead in writing the manuscript, while ZN, ZC, and CF played vital roles in conducting the literature review, collecting and analyzing the data. KC and YS were responsible for conceptualizing the study, analyzing the data, critically reviewing the content, and providing valuable revisions to the manuscript.

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Correspondence to Kai Chen or Yaqin Shi.

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Lu, L., Niu, Z., Chao, Z. et al. Exploring the therapeutic potential of ADC combination for triple-negative breast cancer. Cell. Mol. Life Sci. 80, 350 (2023). https://doi.org/10.1007/s00018-023-04946-x

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