Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates

American Society of Clinical Oncology Educational Book, Journal Year: 2024, Volume and Issue: 44(3)

Published: June 1, 2024

Antibody-drug conjugates (ADCs) have reshaped the cancer treatment landscape across a variety of different tumor types. ADCs' peculiar pharmacologic design combines cytotoxic properties chemotherapeutic agents with selectivity targeted therapies. At present, approval many ADCs used in clinical practice has not always been biomarker-driven. Indeed, predicting activity and toxicity through demonstration specific biomarkers is still great unmet need, identification patients who can derive significant benefit from may often be uncertain. With lack robust predictive to anticipate primary, intrinsic resistance no consolidated aid early (ie, acquired resistance), determination precise biologic mechanisms ADC safety becomes priority quest for better patient-centric outcomes. Of relevance, whether target antigen expression determinant primary clarified, available data remain quite controversial. Antigen assessment typically performed on tissue biopsy, hence only providing information site, therefore unable capture heterogeneous patterns expression. Quantifying all sites would help understand heterogeneity, whereas molecularly characterizing tumor-intrinsic features over time might provide mechanisms. In addition, represent critical concern, since most profile that resembles chemotherapies, unique adverse events requiring special management, possibly because differential pharmacokinetics between small-molecule agent versus payload similar class (eg, deruxtecan conjugate–related interstitial lung disease). As such, potential improve patient selection enrich population likely substantial benefit, especially those disease settings where happen approved competing indications, undefined make decision making unclear how sequence ADCs. this point, clinically actionable space remains top research priority.

Language: Английский

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HER2-low gastric cancer: is the subgroup targetable?

ESMO Open, Journal Year: 2024, Volume and Issue: 9(9), P. 103679 - 103679

Published: Aug. 23, 2024

Therapeutic developments in the targeting of human epidermal growth factor receptor 2 (HER2)-expressing gastric cancer have followed dramatic success HER2-expressing breast treatment, which has facilitated expansion indications for anti-HER2 agents to include not only conventional HER2-positive cancer, but also HER2-low and HER2-ultralow subgroups. The targetability however, yet be established. Hence, further studies are needed comprehensively understand clinicopathological features, specific gene alterations, distinct tumor immune microenvironment compare them with those or -negative cancer. Antibody-drug conjugates HER2 play an important role making targetable. In this context, a deeper understanding novel agents, including antibody-drug conjugates, bispecific T-cell engager antibodies, combination these as well new forms immunomodulatory required. Redefining re-categorizing status through immunohistochemistry/fluorescence situ hybridization evaluating ERRB2 copy number gain protein overexpression levels measured using DNA RNA sequencing might helpful identifying populations tumors who would ideally benefit from treatment. current paper reviewed recent clinical trials, focusing particularly on together basic/translational findings, discuss perspectives therapeutic development treatment subgroup.

Language: Английский

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Predicting Response to Antibody Drug Conjugates: A Focus on Antigens’ Targetability

The Oncologist, Journal Year: 2023, Volume and Issue: 28(11), P. 944 - 960

Published: Sept. 4, 2023

Abstract Antibody-drug conjugates (ADCs) represent a cornerstone in the treatment of many cancers nowadays. ADCs fulfill their function by binding target on tumor cell membrane to deliver cytotoxic payload; addition, those moieties capable crossing cancer membranes can achieve near-by cells that do not express antigen, exerting so-called “bystander” effect. The presence specific antigen expressed has been for long considered crucial and commonly required inclusion patients clinical trials with ADCs. To date, only ado-trastuzumab-emtansine, fam-trastuzumab deruxtecan-nxki, mirvetuximab soravtansine-gynx are approved according expression solid tumors, while use other (eg, sacituzumab govitecan) is conditioned biomarker. Given ever-growing number under investigation, it essential find new biomarkers guide use, especially settings which different establish best therapeutic sequence based robust biomarkers. Hence, this work addresses role antigens predicting response ADCs, focusing examples antigens’ targetability cells’ surface or aberrations mutation over-expression). New methods assessment quantification targets’ expression, like molecular imaging vitro assays, might be key tools improve biomarker analysis eventually better outcomes refined patient selection.

Language: Английский

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Synergizing Immunotherapy and Antibody–Drug Conjugates: New Horizons in Breast Cancer Therapy

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(9), P. 1146 - 1146

Published: Aug. 29, 2024

The advent of immunotherapy and antibody–drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance limited efficacy in certain cases, remain. Recently, the combination these therapies has emerged a promising approach address challenges. ADCs play crucial role by delivering cytotoxic agents directly cells, minimizing damage healthy tissue enhancing tumor-killing effect. Concurrently, immunotherapies harness body’s immune system recognize eliminate cells. This integration offers potential overcome mechanisms significantly improve therapeutic outcomes. review explores rationale behind combining with ADCs, recent advances this field, implications for treatment.

Language: Английский

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Emerging Toxicities of Antibody-Drug Conjugates for Breast Cancer: Clinical Prioritization of Adverse Events from the FDA Adverse Event Reporting System

Targeted Oncology, Journal Year: 2024, Volume and Issue: 19(3), P. 435 - 445

Published: May 1, 2024

Language: Английский

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Monitoring and management of adverse effects associated with trastuzumab deruxtecan: a UAE-specific consensus

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 15, 2025

Breast cancer is the most frequently diagnosed in UAE and a leading cause of cancer-related mortality. Although early diagnosis contributes to favorable prognoses, novel treatment modalities like antibody-drug conjugates (ADCs) have significantly broadened therapeutic landscape for patients metastatic settings. The recognition "HER2-low" expression as targetable category has caused paradigm shift management breast cancer. initially developed target HER2-positive cancer, trastuzumab deruxtecan (T-DXd), an ADC, now also been approved treat or unresectable HER2-low cancers. Despite inherent specificity risk off-site toxicity exists essential component while assessing risk-benefit ratio treatment. Developing strategies balance efficacy safety crucial, especially newly therapies T-DXd. Regional perspectives, cultural beliefs, demographic factors influence decisions outcomes. objective this paper establish UAE-specific consensus among oncologists on practical T-DXd considerations associated side effects. Establishing monitoring managing effects experts can promote informed decision-making.

Language: Английский

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HER2-Low Breast Cancer—Current Knowledge and Future Directions

Medicina, Journal Year: 2025, Volume and Issue: 61(4), P. 644 - 644

Published: April 1, 2025

The concept of binary classification HER2 status has recently been challenged following the DESTINY-Breast trial data showing a clinically meaningful response to antibody–drug conjugates (ADCs) in invasive breast cancer expressing low levels HER2. HER2-low is defined as an immunohistochemistry (IHC) score 1+ and 2+ without gene amplification. While does not represent biological entity, it encompasses both hormone receptor-positive triple-negative cancer. Differences exist between this group HER2-null In review, we provide update on HER2-ultralow cancer, including background data, evolution expression, current clinical guidelines, quality issues, future directions.

Language: Английский

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Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(7), P. 1873 - 1873

Published: March 24, 2024

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% female cases are HER2-positive, the majority being HR-positive. These tumors show cross-talk between hormonal HER2 pathways; interaction has implications for treatment options disease. In this review, we analyze biology HR-positive/HER2-positive summarize evidence concerning standard care both in neoadjuvant/adjuvant settings advanced Additionally, focus on new trials drugs entity: HER2-low cancer.

Language: Английский

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Use of Antibody–Drug Conjugates in the Early Setting of Breast Cancer

Clinical Medicine Insights Oncology, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 1, 2024

Antibody–drug conjugates (ADCs) are anticancer agents with the capacity to selectively deliver their payloads cancer cells. consist of a monoclonal antibody backbone connected by linker cytotoxic payloads. conjugate effect occurs either directly targeting cells via membrane antigen or through “bystander effect.” have demonstrated efficacy against various types tumors, including breast cancer. Ado-trastuzumab emtansine is presently only approved ADC for treatment in early setting, while several ADCs now metastatic Due transformative impact that reported setting advanced cancer, researchers testing more such compounds portend benefits patients highly potent drugs. Ongoing trials hold potential transform protocols near future. These aiming at evaluating different modulation approaches, as informed risk recurrence, toward de-escalation. Efforts provided ongoing clinical identify who will benefit most, pursue paradigms precision medicine novel ADCs. This review focuses on role providing an overview latest progress development and how they implemented trials.

Language: Английский

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Think “HER2” different: integrative diagnostic approaches for HER2-low breast cancer

Pathologica, Journal Year: 2023, Volume and Issue: 115(6), P. 292 - 301

Published: Dec. 1, 2023

This work explores the complex field of HER2 testing in HER2-low breast cancer era, with a focus on methodological aspects. We aim to propose clear positions scientific societies, institutions, pathologists, and oncologists guide shape appropriate diagnostic strategies for cancer. The fundamental question at hand is whether necessary tools effectively translate our knowledge about into practical schemes lower spectrum expression are available. Our investigation centered significance distinguishing between an immunohistochemistry (IHC) score 0 1+ light clinical implications now apparent, as patients become eligible trastuzumab-deruxtecan treatment. Furthermore, we discuss definition beyond its conventional boundaries assess reliability established procedures designed time when therapeutic perspectives were non-existent these cases. In this regard, examine potential complementary technologies, such gene analysis liquid biopsy. Ultimately, consider role artificial intelligence (AI) digital pathology integration testing, particular emphasis application context

Language: Английский

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