Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer

Yi, Cao; Li, Yunjin; Liu, Ruijie; Zhou, Jianhua; Wang, Kuansong

doi:10.3390/cancers15092568

Cited by 5 publications

(3 citation statements)

References 139 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of HER2, found in 15–30% of all breast cancers, is associated with metastasis and poor prognosis. Targeting of HER2 has greatly increased patient survival in breast cancer, but development of drug resistance is still a major therapeutic obstacle [ 313 ]. A recent study by Hansen et al showed that overexpression of HER2 was associated with invasion-promoting peripheral localization of lysosomes [ 314 ].…”

Section: Lysosomal Involvement In Cancermentioning

confidence: 99%

Lysosomes in Cancer—At the Crossroad of Good and Evil

Eriksson,

Öllinger

2024

Cells

View full text Add to dashboard Cite

Although it has been known for decades that lysosomes are central for degradation and recycling in the cell, their pivotal role as nutrient sensing signaling hubs has recently become of central interest. Since lysosomes are highly dynamic and in constant change regarding content and intracellular position, fusion/fission events allow communication between organelles in the cell, as well as cell-to-cell communication via exocytosis of lysosomal content and release of extracellular vesicles. Lysosomes also mediate different forms of regulated cell death by permeabilization of the lysosomal membrane and release of their content to the cytosol. In cancer cells, lysosomal biogenesis and autophagy are increased to support the increased metabolism and allow growth even under nutrient- and oxygen-poor conditions. Tumor cells also induce exocytosis of lysosomal content to the extracellular space to promote invasion and metastasis. However, due to the enhanced lysosomal function, cancer cells are often more susceptible to lysosomal membrane permeabilization, providing an alternative strategy to induce cell death. This review summarizes the current knowledge of cancer-associated alterations in lysosomal structure and function and illustrates how lysosomal exocytosis and release of extracellular vesicles affect disease progression. We focus on functional differences depending on lysosomal localization and the regulation of intracellular transport, and lastly provide insight how new therapeutic strategies can exploit the power of the lysosome and improve cancer treatment.

show abstract

Section: Lysosomal Involvement In Cancermentioning

confidence: 99%

Lysosomes in Cancer—At the Crossroad of Good and Evil

Eriksson,

Öllinger

2024

Cells

View full text Add to dashboard Cite

show abstract

“…This approach has revolutionized cancer treatment, leading to improved survival rates and reduced toxicity compared to traditional chemotherapy (10,11). Medicines such as imatinib, which cures chronic myeloid leukemia, and trastuzumab, which treats HER2-positive breast cancer, are prime examples of how medicinal chemistry has revolutionized treatments for cancer (12,13). Moreover, medicinal chemistry has been pivotal in developing antiviral drugs, particularly during the ongoing COVID-19 pandemic (14,15).…”

Section: Dear Editormentioning

confidence: 99%

Medicinal Chemistry is Shaping the World of Therapy

Muhammad

2024

J Kermanshah Univ Med Sci

View full text Add to dashboard Cite

“…Resistance to targeted therapies is a significant challenge in BCa treatment ( 157 ). BsAbs can potentially target multiple signaling pathways simultaneously, addressing resistance mechanisms and improving treatment responses in resistant or refractory BCa cases ( 7 , 158 ). BsAbs have the advantage of explicitly targeting cancer cells and sparing normal cells, potentially reducing off-target toxicities associated with non-specific treatments ( 80 ).…”

Section: Challenges and Opportunitiesmentioning

confidence: 99%

Bispecific antibodies revolutionizing breast cancer treatment: a comprehensive overview

Lan,

Chen,

Yao

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Breast cancer (BCa) is known as a complex and prevalent disease requiring the development of novel anticancer therapeutic approaches. Bispecific antibodies (BsAbs) have emerged as a favorable strategy for BCa treatment due to their unique ability to target two different antigens simultaneously. By targeting tumor-associated antigens (TAAs) on cancer cells, engaging immune effector cells, or blocking critical signaling pathways, BsAbs offer enhanced tumor specificity and immune system involvement, improving anti-cancer activity. Preclinical and clinical studies have demonstrated the potential of BsAbs in BCa. For example, BsAbs targeting human epidermal growth factor receptor 2 (HER2) have shown the ability to redirect immune cells to HER2-positive BCa cells, resulting in effective tumor cell killing. Moreover, targeting the PD-1/PD-L1 pathway by BsAbs has demonstrated promising outcomes in overcoming immunosuppression and enhancing immune-mediated tumor clearance. Combining BsAbs with existing therapeutic approaches, such as chemotherapy, targeted therapies, or immune checkpoint inhibitors (ICIs), has also revealed synergistic effects in preclinical models and early clinical trials, emphasizing the usefulness and potential of BsAbs in BCa treatment. This review summarizes the latest evidence about BsAbs in treating BCa and the challenges and opportunities of their use in BCa.

show abstract

Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer

Cited by 5 publications

References 139 publications

Lysosomes in Cancer—At the Crossroad of Good and Evil

Lysosomes in Cancer—At the Crossroad of Good and Evil

Medicinal Chemistry is Shaping the World of Therapy

Bispecific antibodies revolutionizing breast cancer treatment: a comprehensive overview

Contact Info

Product

Resources

About