[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-349608-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-349608-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","the-phosphatidylinositol-3-kinase-pi3k-inhibitor-inavolisib-has-breast-cancer-synergy-combined-with-recombinant-methioninase-but-not-on-normal-cells","The Phosphatidylinositol 3-Kinase (PI3K) Inhibitor Inavolisib Has Breast-cancer Synergy Combined With Recombinant Methioninase But Not on Normal Cells","","The PI3K pathway is implicated in oncogenesis, yet therapies targeting mutated PI3K signaling often show limited efficacy. This study evaluates whether the PI3K inhibitor inavolisib (IVB) produces synergistic effects with recombinant methioninase (rMETase) in breast-cancer cells compared with normal fibroblasts. Cell viability was measured using a WST-8 assay to determine IC50 values and to assess combination effects at IC50 doses.",{"@graph":14,"@context":72},[15,34,55],{"@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/the-phosphatidylinositol-3-kinase-pi3k-inhibitor-inavolisib-has-breast-cancer-synergy-combined-with-recombinant-methioninase-but-not-on-normal-cells/349608/",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/the-phosphatidylinositol-3-kinase-pi3k-inhibitor-inavolisib-has-breast-cancer-synergy-combined-with-recombinant-methioninase-but-not-on-normal-cells/349608.png","ImageObject",300,407,{"name":42,"@type":43},"anakgang17","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":22},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What was the main purpose of combining inavolisib with recombinant methioninase?","Question",{"text":62,"@type":63},"To determine whether IVB shows synergy with rMETase on breast-cancer cells compared with normal fibroblasts.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How were drug effects quantified in this study?",{"text":67,"@type":63},"Cell viability was measured using the WST-8 cell-viability assay, and IC50 values for IVB and rMETase were determined in vitro.",{"name":69,"@type":60,"acceptedAnswer":70},"Did the IVB and rMETase combination work similarly in cancer cells and normal cells?",{"text":71,"@type":63},"No. The combination was synergistic on MCF-7 breast-cancer cells but not synergistic on Hs-27 normal fibroblasts.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},349608,1790126520,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":22,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":106,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","doi: 10.21873/invivo.14420  \nThe Phosphatidylinositol 3‑Kinase (PI3K) Inhibitor Inavolisib Has Breast‑cancer Synergy Combined With Recombinant Methioninase But Not on Normal Cells  \nJINSOO KIM1,2,3, QINGHONG HAN1, SHUKUAN LI1, YUTA MIYASHI1,2, TOMOYUKI ISHIGURO1,2, MICHAEL BOUVET2 and ROBERT M. HOFFMAN1,2  \n1AntiCancer Inc., San Diego, CA, U.S.A.;  \n2 Department of Surgery, University of California, San Diego, CA, U.S.A.;  \n3 Department of Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea  \nAbstract  \nBackground/Aim: The phosphatidylinositol 3‑Kinase (PI3K) pathway is thought tobe oncogenic in cancers when it is mutated at various sites. However, drugs targeting this mutated pathway have had only modest efficacy. Recently, anew inhibitor targeting the PI3K pathway, inavolisib (IVB), has been developed. In the present study, we determined whether IVB is synergistic with recombinant methioninase (rMETase) on breast‑cancer cells compared to normal fibroblasts.  \nMaterials and Methods: Cell viability was determined using the WST‑8 cell‑viability assay. The half‑maximal inhibitory concentrations (IC50) ofIVB and rMETase were determined on MCF‑7 human breast‑cancer cells compared to Hs‑27 human normal fibroblasts in vitro. The efficacy of rMETase combined with IVB, at their respective IC50 values, on MCF-7 breast-cancer cells and Hs-27 normal fibroblasts was evaluated.  \nResults: The IC50 of IVB on MCF-7 breast-cancer cells of 83 nM was significantly lower than the IC50 on Hs‑27 normal fibroblasts, which was 8.8 μM. The combination of rMETase and IVB was synergistic on MCF-7 breast-cancer cells, resulting inan inhibition of 76.2%. In contrast, the combination of rMETaseand IVB was not synergistic on Hs‑27 normal fibroblasts.  \nConclusion: IVB had a very low IC50 on MCF-7 breast-cancer cells compared to Hs-27 normal fibroblasts. IVB had increased efficacy on MCF-7 breast-cancer cells when combined with rMETase, showing strong synergy. In contrast, the combination of rMETase and IVB showed no synergy on Hs-27 normal fibroblasts. Therefore, IVB in combination with rMETase has strong clinical potential for breast cancer and possibly other cancers.  \nKeywords: Inavolisib, PI3K inhibitor, methionine addiction, Hoffman effect, recombinant methioninase, synergy, MCF-7, breast-cancer cells, Hs-27 normal fibroblasts.  \n✉ Robert M. Hoffman, PhD, AntiCancer, Inc., 7917 Ostrow Street, Suite B, San Diego, CA 92111, U.S.A. Tel: +1 6198852284,  \ne‑mail: [all@anticancer.com](all@anticancer.com)  \nReceived May 6, 2026 | Revised June 8, 2026 | Accepted June 9, 2026  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n©2026 The Author(s) . Published by the International Institute of Anticancer Research.  \nIntroduction  \nThe phosphatidylinositol 3‑kinase (PI3K), protein kinase B/AKT, and mammalian-target-of-rapamycin (mTOR) pathways, collectively known as the PI3K/AKT/mTOR pathway, are thought to be involved with oncogenesis (1) . 29% of breast cancers and 40% of HR+/HER-2 breast cancers have a mutation in PI3K (1-3) . Inhibitors of PI3K have been developed over many years and are in clinical trials, including taselisib, alpelisib, buparlisib, and pictilisib (2) .  \nRecently, inavolisib (IVB), a novel PI3K inhibitor that also selectively induces degradation of PI3Kα, the catalytic subunit of PI3K, has been developed (2) . IVB has more than 300-fold selectivity for mutant PI3Kα and is being evaluated in phase III clinical trials for PIK3CA-mutated breast cancer (2). IVB is also currently being investigated in another clinical trial to confirm its efficacy in combination with other agents (3) .  \nMethionine addiction is a general and fundamental hallmark of cancer and is due, at least in part, to excessive and aberrant transmethylation reactions in cancer cells. Methion","cbCaiidicKDTzAHz","https://ap.wps.com/l/cbCaiidicKDTzAHz","pdf",693906,"English","# Abstract\n## Background/Aim\n## Materials and Methods\n## Results\n## Conclusion\n# Introduction\n# Materials and Methods\n## Cell culture\n## Recombinant methioninase production\n## Reagents\n## Cell viability assay","[{\"question\":\"What was the main purpose of combining inavolisib with recombinant methioninase?\",\"answer\":\"To determine whether IVB shows synergy with rMETase on breast-cancer cells compared with normal fibroblasts.\"},{\"question\":\"How were drug effects quantified in this study?\",\"answer\":\"Cell viability was measured using the WST-8 cell-viability assay, and IC50 values for IVB and rMETase were determined in vitro.\"},{\"question\":\"Did the IVB and rMETase combination work similarly in cancer cells and normal cells?\",\"answer\":\"No. The combination was synergistic on MCF-7 breast-cancer cells but not synergistic on Hs-27 normal fibroblasts.\"}]","The Phosphatidylinositol 3-Kinase (PI3K) Inhibitor Inavolisib Has Breast-cancer Synergy Combined With Recombinant Methioninase But Not on Normal Cells | PDF",1790084492,18]