The medical research field has been tremendously galvanized to improve the prediction of therapy efficacy by the revolution in artificial intelligence (AI). An earnest desire to find better ways to predict the effectiveness of therapy with the use of AI has propelled the evolution of new models in which it can become more applicable in clinical settings such as breast cancer detection. However, in some instances, the U.S. Food and Drug Administration was obliged to back some previously approved inaccurate models for AI-based prognostic models because they eventually produce inaccurate prognoses for specific patients who might be at risk of heart failure. In light of instances in which the medical research community has often evolved some unrealistic expectations regarding the advances in AI and its potential use for medical purposes, implementing standard procedures for AI-based cancer models is critical. Specifically, models would have to meet some general parameters for standardization, transparency of their logistic modules, and avoidance of algorithm biases. In this review, we summarize the current knowledge about AI-based prognostic methods and describe how they may be used in the future for predicting antibody-drug conjugate efficacy in cancer patients. We also summarize the findings of recent late-phase clinical trials using these conjugates for cancer therapy.
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http://dx.doi.org/10.3390/cancers16173089 | DOI Listing |
Expert Opin Biol Ther
January 2025
OU Stephenson Cancer Center, Oklahoma City.
Introduction: Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Oncology, University Hospital of Udine, 33100 Udine, Italy.
Antibody-drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (), human epidermal growth factor receptor 3 (), trophoblast cell surface antigen 2 (), Mesenchymal-epithelial transition factor (), and carcinoembryonic antigen-related cell adhesion molecule 5 (). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs.
View Article and Find Full Text PDFJ Immunother Cancer
December 2024
Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA
Background: Granzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. Fusion proteins and immunoconjugates represent an innovative therapeutic approach to specifically deliver a deadly payload to target cells. Epithelial membrane protein-2 (EMP2) is highly expressed in invasive breast cancer (BC), including triple-negative BC (TNBC), and represents an attractive therapeutic target.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFPLoS One
January 2025
Worldwide Health Economics and Outcomes Research, Bristol Myers Squibb, Princeton, NJ, United States of America.
Background: Belatacept is approved for the prophylaxis of organ rejection in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients and is associated with a risk of post-transplant lymphoproliferative disorder (PTLD).
Methods: Data from the Organ Procurement and Transplantation Network were used to examine patterns of belatacept use, describe patient characteristics, and estimate risk of PTLD in EBV-seropositive, kidney-only transplant recipients receiving belatacept- or calcineurin inhibitor (CNI)-based immunosuppression as part of US Food and Drug Administration-mandated safety monitoring.
Results: During the study period (June 15, 2011-June 14, 2016), 94.
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