Breast

• Antibody drug conjugates (ADCs) are a class of targeted cancer therapies that combine monoclonal antibodies with cytotoxic payloads
• ADCs selectively deliver cytotoxic therapies to cancer cells expressing specific surface antigens, such as HER2
• References: Cancers (Basel) 2021;13:2898, Nat Rev Cancer 2012;12:252

• In breast cancer, several ADCs have been developed and approved, with others in various stages of clinical development
• ADCs are targeted therapies that link monoclonal antibodies to cytotoxic agents, allowing precise delivery of drugs to cancer cells with specific antigens; this approach improves treatment effectiveness while minimizing systemic toxicity compared to traditional chemotherapy
• References: Ann Oncol 2015;26:v8, Eur J Cancer 2020;135:66, Int J Mol Sci 2023;24:13726

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Antibody drug conjugates (ADCs) have revolutionized cancer therapeutics by delivering cytotoxic medications with reduced toxicity to healthy tissues. What are some of the challenges and strategies being explored in ADC therapy for breast cancer?

1. Avoiding personalized treatment strategies based on molecular profiling of individual cancer cells
2. Development of strategies to prevent side effects in healthy tissues by using higher doses of ADCs
3. Limiting the use of ADCs only to patients with HER2 positive breast cancer
4. Overcoming resistance mechanisms and utilizing combinatorial approaches with other agents

D. Overcoming resistance mechanisms and utilizing combinatorial approaches with other agents, such as immune checkpoint inhibitors (ICIs) and targeted tyrosine kinase inhibitors (TKIs). Preclinical studies have shed light on potential resistance mechanisms, emphasizing the potential benefit of combinational approaches with other agents, such as immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, to enhance treatment effectiveness. Answer B is incorrect because higher doses of ADCs can increase toxicity, rather than prevent side effects. The focus is on precise targeting to minimize off target effects, not increasing dosage. Answer C is incorrect because ADCs are not limited to HER2 positive breast cancer. Newer ADCs are being developed for other targets such as TROP2. Answer A is incorrect because ADC therapy is a personalized treatment designed to target specific antigens expressed on tumor cells (Int J Mol Sci 2023;24:13726).

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Reference: Antibody drug conjugate therapy

In which scenario would antibody drug conjugates (ADCs) be indicated for breast cancer treatment?

1. ADCs are indicated for all breast cancer patients regardless of the expression of surface antigens
2. ADCs are indicated for patients whose cancer cells express specific antigens that can be targeted by monoclonal antibodies
3. ADCs are primarily used for patients who do not respond to traditional chemotherapy, without consideration of antigen expression
4. ADCs are only used when cancer cells lack any receptors for internalization, relying solely on nonspecific pinocytosis for drug uptake

B. ADCs are indicated for patients whose cancer cells express specific antigens that can be targeted by monoclonal antibodies. ADCs are indicated for patients whose cancer cells express specific antigens, such as HER2, that can be targeted by monoclonal antibodies. Answer A is incorrect because ADCs are not indicated for all breast cancer patients; they are only effective if the tumor expresses the target antigen. Answer C is incorrect because the use of ADCs is not solely dependent on a lack of response to traditional chemotherapy; it depends on the presence of specific target antigens. Answer D is incorrect because ADC therapy relies on receptor mediated internalization for efficient drug delivery to cancer cells (Int J Mol Sci 2023;24:13726).

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Reference: Antibody drug conjugate therapy