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Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.

J Transl Med

January 2025

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, No.651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.

Background: HER2-targeted antibody-drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.

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Background: Breast cancer is the leading cause of cancer among women globally and the most common cancer among women in Sierra Leone. This study aimed to evaluate the patterns of clinical presentation, management and outcomes among breast cancer patients who presented at the Connaught Teaching Hospital Complex in Sierra Leone.

Method: A retrospective, cross-sectional study was conducted at the specialist outpatient clinic at the Connaught Hospital.

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Triple-negative breast cancer (TNBC) is one of the most fatal malignancies in the world, accounting for 42% of all deaths due to metastasis. The significant development is hindered by the multi-drug resistance and poor patient compliance. PIK3CA gene mutation is one of the important causes of TNBC, which causes dysregulation of the cell cycle and cell proliferation.

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Colorectal cancer (CRC) is among the most common cancer types for both sexes. Tripartite motif 36 (TRIM36) has been reported to be aberrantly expressed in several cancer types, suggesting its involvement in cancer progression. However, the role of TRIM36 in the colorectal carcinogenesis remain unknown.

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Most of the triple negative phenotype or basal-like molecular subtypes of breast cancers are associated with aggressive clinical behaviour and show poor disease prognosis. Current treatment options are constrained, emphasizing the need for novel combinatorial therapies for this particular tumor subtype. Our group has demonstrated that functionally active p21 activated kinase 1 (PAK1) exhibits significantly higher expression levels in clinical triple negative breast cancer (TNBC) samples compared to other subtypes, as well as adjacent normal tissues.

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