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Signalomics is proposed as a fast, robust functional approach to assess oncogenic signaling pathway activity in fresh tumors, using transcriptional reporters to guide and validate targeted therapy sensitivity, thereby strengthening MTB workflows and refining clinical decisions for breast and gynecological cancers.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/signalomics-for-molecular-tumor-boards-and-precision-oncology-of-breast-and-gynecological-cancers/371722/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/signalomics-for-molecular-tumor-boards-and-precision-oncology-of-breast-and-gynecological-cancers/371722.png","ImageObject",300,407,{"name":42,"@type":43},"Stanford","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What problem do molecular tumor boards (MTBs) aim to solve in precision oncology?","Question",{"text":63,"@type":64},"MTBs integrate molecular and clinical assessment to select personalized treatments more quickly by identifying actionable features in individual cancer cases.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why is Signalomics proposed alongside MTB workflows?",{"text":68,"@type":64},"Cancer driver activity can be mutation-independent and not all deleterious mutations are truly pathogenic, so a functional readout of oncogenic pathway overactivation can complement genomic profiling.",{"name":70,"@type":61,"acceptedAnswer":71},"How does Signalomics assess signaling pathway activity and guide treatment decisions?",{"text":72,"@type":64},"It uses transcriptional reporters in primary tumor cells to identify pathways overactivated in a tumor and validate sensitivity to targeted therapies, producing actionable insights for treatment 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V Denisenko1,6, Anna E Ivanova1,6, Alexey Koval 2, Denis N Silachev1,2,3, Lee Jia4, Gennadiy T Sukhikh1 & Vladimir L Katanaev 2,5 ✉  \nAbstract  \nPrecision oncology led to the establishment and widespread application of molecular tumor boards (MTBs)—multidisciplinary units combining molecular and clinical assessment of individual cancer cases for swift selection of personalized treatments. Whole-exome or gene panel sequencing, combined with transcriptomic, immunohistochemical, and other molecular analyses, often permits dissection of molecular drivers of a tumor and identification of its potential targetable vulnerabilities, instructing clinical oncologists on sometimes unconventional treatment options. However, cancer drivers are often unleashed mutation-independently, especially in breast and gynecological cancers, and deleterious mutations are not always pathogenic. To complement the MTB arsenal, we chart here the molecular toolset we call Signalomics that permits fast and robust assessment of a panel of oncogenic signaling pathways in fresh tumor samples. Using transcriptional reporters introduced in primary tumor cells, this approach identifies the pathways overactivated in a given tumor and validates their sensitivity to targeted therapies, providing actionable insights for personalized treatment strategies. Integration of Signalomics into MTB workflows bridges the gap between molecular profiling and functional pathway analysis, refining clinical treatment decisions and advancing precision oncology.  \nKeywords Molecular Tumor Board; Oncogenic Signaling Pathways; Signalomics; Precision Oncology; Breast and Gynecological Cancers  \nB  \nreast cancer (BC) and gynecological cancers, including ovarian (OC), cervical (CC), and endometrial cancer  \n(EC), are among the leading mortality and morbidity cases in women and represent significant medical, social, and economic challenges (Bray et al, 2024; Kerr et al, 2021) . The 5-year overall survival rate for OC patients remains ~47%, with over 70% of cases being diagnosed at advanced stages. CC ranks fourth among the most common cancers in women globally, posing a significant health burden, especially in developing countries. EC, primarily affecting postmenopausal women, is the sixth most common female cancer. Advanced andrecurrent gynecological cancers are associated with poor prognosis and lack of effective treatments (Wang et al, 2020) . BC, on the other hand, holds the highest incidence and mortality rates among all cancer types affecting women, and is the most frequent type of cancer in general ([who.int/initiatives/global-breast-cancer](who.int/initiatives/global-breast-cancer)initiative) .  \nStandard treatment approaches for breast and gynecological cancers involve a combination of surgery, chemotherapy, and radiation therapy, primarily aimed at suppressing tumor growth without specifically targeting the molecular drivers of the disease (Nie et al, 2020) . However, thenon-specific nature of cell death caused by  \nthese treatments can lead to harmful side effects. Insufficiency of available targeted therapeutic strategies has contributed to the high mortality rates in patients with these cancers (Heintz et al, 2006) . In recent years, the development of molecular diagnostics utilizing next-generation sequencing (NGS) has allowed comprehensive tumor profiling to enable personalized medicine approaches, engaging the power of targeted therapies that directly address the molecular drivers of cancer (Deans et al, 2017; Weberpals et al, 2011) .  \nDifferent targeted therapies are available for BC, depending on the tumor subtype: estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-positive (HER2+), and triple-negative breast cancer (TNBC) (Polyak and Metzger Filho, 2012) . Thus, ER+ tumors are commonly treated with anti-hormonal therapy to suppress estroge","cbCailBhs6tDvVdy","https://ap.wps.com/l/cbCailBhs6tDvVdy","pdf",2282690,"English","# Precision oncology and molecular tumor boards\n## Molecular drivers, limitations, and non-pathogenic mutations\n## Signalomics as a functional pathway assessment tool\n## Integration into MTB workflows\n# Breast and gynecological cancer challenges\n## Epidemiology and outcomes\n## Standard treatments and shortcomings\n## Targeted therapies by breast cancer subtype\n# Functional strategy for actionable signaling insights","[{\"question\":\"What problem do molecular tumor boards (MTBs) aim to solve in precision oncology?\",\"answer\":\"MTBs integrate molecular and clinical assessment to select personalized treatments more quickly by identifying actionable features in individual cancer cases.\"},{\"question\":\"Why is Signalomics proposed alongside MTB workflows?\",\"answer\":\"Cancer driver activity can be mutation-independent and not all deleterious mutations are truly pathogenic, so a functional readout of oncogenic pathway overactivation can complement genomic profiling.\"},{\"question\":\"How does Signalomics assess signaling pathway activity and guide treatment decisions?\",\"answer\":\"It uses transcriptional reporters in primary tumor cells to identify pathways overactivated in a tumor and validate sensitivity to targeted therapies, producing actionable insights for treatment selection.\"}]","Signalomics for Molecular Tumor Boards and Precision Oncology of Breast and Gynecological Cancers | PDF",1790192705]