Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions

Kumari, Shivangi; Raj, Sonam; Babu, M. Arockia; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh

doi:10.1007/s12272-023-01479-6

Cited by 4 publications

(1 citation statement)

References 179 publications

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“…Recently, antibody–drug conjugates (ADCs) have gained attention for the development of antitumor drugs. These compounds preserve the potent cytotoxic properties of natural substances with the precise targeting of antibodies, achieving the elimination of tumor cells in an effective and precise manner [ 64 ]. In fact, two of the three marine sponge-derived drugs currently in clinical trials are ADCs.…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Natural Products Derived from Marine Sponges with Antitumor Potential against Lung Cancer: A Systematic Review

Ortigosa-Palomo,

Quiñonero,

Ortiz

et al. 2024

Marine Drugs

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Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.

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Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Natural Products Derived from Marine Sponges with Antitumor Potential against Lung Cancer: A Systematic Review

Ortigosa-Palomo,

Quiñonero,

Ortiz

et al. 2024

Marine Drugs

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Antibody-Drug Conjugates in Urothelial Cancer: From Scientific Rationale to Clinical Development

Kwon,

Lee,

Jeong

et al. 2024

Cancers

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Antibody-drug conjugates (ADCs) have been a significant advancement in cancer therapy, particularly for urothelial cancer (UC). These innovative treatments, originally developed for hematological malignancies, use target-specific monoclonal antibodies linked to potent cytotoxic agents. This rational drug design efficiently delivers cancer cell-killing agents to cells expressing specific surface proteins, which are abundant in UC owing to their high antigen expression. UC is an ideal candidate for ADC therapy, as it enhances on-target efficacy while mitigating systemic toxicity. In recent years, considerable progress has been made in understanding the biology and mechanisms of tumor progression in UC. However, despite the introduction of immune checkpoint inhibitors, advanced UC is characterized by rapid progression and poor survival rates. Targeted therapies that have been developed include the anti-nectin 4 ADC enfortumab vedotin and the fibroblast growth factor receptor inhibitor erdafitinib. Enfortumab vedotin has shown efficacy in prospective studies in patients with advanced UC, alone and in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also demonstrated effectiveness in single-armed studies. This review highlights the mechanism of action of ADCs, their application in mono- and combination therapies, primary mechanisms of resistance, and future perspectives for their clinical use in UC treatment. ADCs have proven to be an increasingly vital component of the therapeutic landscape for urothelial carcinoma, filling a gap in the treatment of this progressive disease.

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Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

Medina Pérez,

Baselga,

Schuhmacher

2024

Cancers

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Background: Antibody–drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due to acquired resistance and potential side effects. Objectives: This study focuses on advances in various ADC components to improve both the efficacy and safety of these agents, and includes the analysis of several novel ADC formats. This work assesses whether the unique features of VHHs—such as their small size, enhanced tissue penetration, stability, and cost-effectiveness—make them a viable alternative to conventional antibodies for ADCs and reviews their current status in ADC development. Methods: Following PRISMA guidelines, this study focused on VHHs as components of ADCs, examining advancements and prospects from 1 January 2014 to 30 June 2024. Searches were conducted in PubMed, Cochrane Library, ScienceDirect and LILACS using specific terms related to ADCs and single-domain antibodies. Retrieved articles were rigorously evaluated, excluding duplicates and non-qualifying studies. The selected peer-reviewed articles were analyzed for quality and synthesized to highlight advancements, methods, payloads, and future directions in ADC research. Results: VHHs offer significant advantages for drug conjugation over conventional antibodies due to their smaller size and structure, which enhance tissue penetration and enable access to previously inaccessible epitopes. Their superior stability, solubility, and manufacturability facilitate cost-effective production and expand the range of targetable antigens. Additionally, some VHHs can naturally cross the blood–brain barrier or be easily modified to favor their penetration, making them promising for targeting brain tumors and metastases. Although no VHH–drug conjugates (nADC or nanoADC) are currently in the clinical arena, preclinical studies have explored various conjugation methods and linkers. Conclusion: While ADCs are transforming cancer treatment, their unique mechanisms and associated toxicities challenge traditional views on bioavailability and vary with different tumor types. Severe toxicities, often linked to compound instability, off-target effects, and nonspecific blood cell interactions, highlight the need for better understanding. Conversely, the rapid distribution, tumor penetration, and clearance of VHHs could be advantageous, potentially reducing toxicity by minimizing prolonged exposure. These attributes make single-domain antibodies strong candidates for the next generation of ADCs, potentially enhancing both efficacy and safety.

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Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions

Cited by 4 publications

References 179 publications

Natural Products Derived from Marine Sponges with Antitumor Potential against Lung Cancer: A Systematic Review

Natural Products Derived from Marine Sponges with Antitumor Potential against Lung Cancer: A Systematic Review

Antibody-Drug Conjugates in Urothelial Cancer: From Scientific Rationale to Clinical Development

Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

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