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Rational multi-pathway combinations are limited by dose-limiting toxicity and tumor heterogeneity, motivating co-targeting approaches that improve precision and coverage. Antibody-drug conjugates can deliver potent payloads to tumor cells, and dual targeting of co-expressed receptor pairs may broaden uptake and enable synergistic drug delivery. Nanotechnology platforms further integrate multiple ligands and payloads while identifying co-targeting receptors such as GPCRs. 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Although rational drug combinations targeting multiple oncogenic pathways hold promise, their clinical utility is often compromised by dose-limiting toxicity and tumor heterogeneity. Antibody-drug conjugates (ADCs) offer an alternative by delivering potent agents directly to tumor cells, thereby reducing systemic toxicity. This approach could be further enhanced by the dual targeting of co-expressed tumor-specific cell surface receptor pairs to broaden tumor coverage and enable the precise delivery of synergistically active drugs. Furthermore, nanotechnology-based carriers extend these concepts by enabling the integration of multiple targeting ligands and payloads into a single drug-delivery platform. Systematic identification and validation of novel co-targeting cell surface receptors, such as G protein-coupled receptors (GPCRs), characterized by high tumor relevance and rapid internalization, may improve tumor coverage and drug uptake in therapy-resistant subpopulations. The outlined strategies are very promising to advance precise and personalized treatment strategies for ovarian cancer. However, dual-receptor approaches remain largely investigational, with limited preclinical validation, and their clinical translation is challenged by receptor heterogeneity, uncertain tumor selectivity, potential off-target effects, and inefficient delivery due to tumor-microenvironment barriers. Furthermore, manufacturing, safety, and regulatory requirements need to be addressed.\u003Cbr>Keywords: dual targeting, ovarian cancer, nanomedicine, active targeting, precision therapy |\n| --- |\n| Introduction\u003Cbr>Although most patients newly diagnosed with ovarian cancer initially enter remission, more than 80% eventually develop resistance to platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors.1 These high rates of acquired resistance and disease recurrence continue to complicate clinical management and limit long-term therapeutic benefit.2,3 Ovarian cancer is a molecularly heterogeneous disease comprising several histological subtypes, including high-grade serous ovarian cancer (HGSOC), endometrioid, clear cell and mucinous carcinomas, each exhibiting distinct genomic landscapes, biological behaviors and therapeutic vulnerabilities.4,5 This challenge is particularly pronounced in HGSOC, which accounts for approximately 70% of all ovarian cancer cases and is characterized by frequent and persistent relapse.6 Consequently, HGSOC remains the predominant focus of investigations into novel targeted therapeutic strategies.7 Despite these efforts, five-year survival rates for patients with advanced-stage disease remain ","cbCaijLC38zYKYEr","https://ap.wps.com/l/cbCaijLC38zYKYEr","pdf",4396656,16,"English","# Abstract\n# Introduction","[{\"question\":\"Why is co-targeting considered for personalized ovarian cancer therapy?\",\"answer\":\"Because ovarian cancer is highly lethal and often develops rapid resistance, while tumor heterogeneity limits the durability of conventional treatments. Co-targeting aims to improve precision, broaden tumor coverage, and support synergistically active drug delivery.\"},{\"question\":\"How do antibody-drug conjugates (ADCs) support receptor co-targeting strategies?\",\"answer\":\"ADCs deliver potent agents directly to tumor cells, reducing systemic toxicity. This delivery can be enhanced through dual targeting of co-expressed receptor pairs.\"},{\"question\":\"What challenges limit clinical translation of dual-receptor approaches?\",\"answer\":\"Dual-receptor strategies face receptor heterogeneity, uncertain tumor selectivity, potential off-target effects, and inefficient delivery due to tumor microenvironment barriers, along with manufacturing, safety, and regulatory requirements.\"}]","Receptor Co-targeting Strategies for Personalized Ovarian Cancer Therapy - Review | PDF",1790133058]