Nanodigmbio Biotechnology on LinkedIn: Prediction of homologous recombination deficiency identifies colorectal…

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The HRDirect tool, developed to predict HR deficiency, outperformed other assays in distinguishing PARPi-sensitive CRC models. Combining HRDirect with immunohistochemical analysis of ATM and RAD51C could improve identification of HRD tumors, offering a significant advance in personalized CRC treatment. \nThe full text link: https://lnkd.in/gRTEE4aT\n#CancerResearch #PARPi #CRC #NGS #Biomarkers","sharedContent":{"@type":"WebPage","headline":"Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition - PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39402170/"},"author":{"name":"Nanodigmbio 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text-color-text-low-emphasis leading-[1.33333] m-0 truncate">  638 followers </p> <span class="!text-xs text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 1mo  </time>  </span> </div>  </div> </div> <div class="ellipsis-menu absolute right-0 top-0 main-feed-activity-card__ellipsis-menu !top-auto !relative !mr-1" data-test-id="main-feed-activity-card__ellipsis-menu"> <div class="collapsible-dropdown flex items-center relative hyphens-auto"> <button class="ellipsis-menu__trigger collapsible-dropdown__button btn-md btn-tertiary cursor-pointer !py-[6px] !px-1 flex items-center rounded-[50%] " aria-expanded="false" aria-label="Open menu" data-tracking-control-name="public_post_ellipsis-menu-trigger" tabindex="0"> <icon class="ellipsis-menu__trigger-icon m-0 p-0 centered-icon" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/671xosfpvk4c0kqtyl87hashi"></icon> </button> <ul class="collapsible-dropdown__list hidden container-raised absolute w-auto 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The HRDirect tool, developed to predict HR deficiency, outperformed other assays in distinguishing PARPi-sensitive CRC models. Combining HRDirect with immunohistochemical analysis of ATM and RAD51C could improve identification of HRD tumors, offering a significant advance in personalized CRC treatment. The full text link: <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FgRTEE4aT&urlhash=N9YU&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/gRTEE4aT</a> <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fcancerresearch&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#CancerResearch</a> <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fparpi&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#PARPi</a> <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fcrc&trk=public_post-text" target="_self" 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class="!text-xs text-color-text-low-emphasis leading-[1.33333] m-0 truncate">  832 followers </p> <span class="!text-xs text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 9mo  </time>  </span> </div>  </div> </div> <div class="ellipsis-menu absolute right-0 top-0 main-feed-activity-card__ellipsis-menu !top-auto !relative !mr-1" data-test-id="main-feed-activity-card__ellipsis-menu"> <div class="collapsible-dropdown flex items-center relative hyphens-auto"> <button class="ellipsis-menu__trigger collapsible-dropdown__button btn-md btn-tertiary cursor-pointer !py-[6px] !px-1 flex items-center rounded-[50%] " aria-expanded="false" aria-label="Open menu" data-tracking-control-name="public_post_ellipsis-menu-trigger" tabindex="0"> <icon class="ellipsis-menu__trigger-icon m-0 p-0 centered-icon" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/671xosfpvk4c0kqtyl87hashi"></icon> </button> <ul class="collapsible-dropdown__list hidden container-raised absolute 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PROSER2 is found to have higher expression in primary tumor cells compared to metastatic tissues. It is shown to be localized in the cell membrane and cytosol, and its overexpression reduces metastatic ability while suppression increases it. PROSER2 interacts with STK25 and PDCD10, and their binding is confirmed. STK25 knockdown enhances metastasis by decreasing p-AMPK levels, while PROSER2 overexpression increases p-AMPK levels. This indicates that PROSER2 suppresses invasion via the STK25-AMPK pathway in PDAC.</p>  </div>  <a href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Fpubmed%2Encbi%2Enlm%2Enih%2Egov%2F38293943%2F%3Ffc%3D20240109121018%26ff%3D20240131124933%26v%3D2%2E18%2E0&urlhash=XZmZ&trk=public_post_feed-article-content" target="_self" data-tracking-control-name="public_post_feed-article-content" data-tracking-will-navigate class="flex flex-col feed-article-content" data-test-id="article-content"> <img alt="New Function Annotation of PROSER2 in Pancreatic Ductal Adenocarcinoma" class="lazy-load w-main-feed-card-media object-cover babybear:max-h-[400px]" data-delayed-url="https://media.licdn.com/dms/image/sync/v2/D5627AQHUbbgkX_eMqw/articleshare-shrink_800/articleshare-shrink_800/0/1712340150309?e=2147483647&v=beta&t=rt_smuPR2qaSOCw_84xsLUsG0E_PKm-HyiG-InPRU38" data-ghost-classes="tw-feed-content-ghost-image" 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Used in conjunction with other analytical tools, like XRC, cryo-EM can provide additional insights into the interactions between molecules. 👨🔬 In a recent study, Nested Therapeutics leveraged cryo-EM to investigate their pan-RAF-MEK <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fmolecularglue&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#molecularglue</a>. While traditional inhibitors targeting the RAS-MAPK pathway have limitations, novel approaches like pan-RAF-MEK molecular glues offer the potential for more effective cancer therapies. 🔬 The use of <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fcryoem&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#cryoEM</a> helped validate the glue's binding to the target protein; revealing a clear density for their molecule within a specific site of MEK1. This finding strongly supports the glue's ability to engage with activated RAF signaling complexes, key drivers of cancer progression. 📑 Read the study now: <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FgGXapyCn&urlhash=Fg2K&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/gGXapyCn</a></p>  </div>  <a href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Fpubmed%2Encbi%2Enlm%2Enih%2Egov%2F38588399%2F&urlhash=fNzF&trk=public_post_feed-article-content" target="_self" data-tracking-control-name="public_post_feed-article-content" data-tracking-will-navigate class="flex flex-col feed-article-content" data-test-id="article-content"> <img alt="The Pan-RAF-MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS-MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers - PubMed" class="lazy-load 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text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 5mo  </time>  </span> </div>  </div> </div> <div class="ellipsis-menu absolute right-0 top-0 main-feed-activity-card__ellipsis-menu !top-auto !relative !mr-1" data-test-id="main-feed-activity-card__ellipsis-menu"> <div class="collapsible-dropdown flex items-center relative hyphens-auto"> <button class="ellipsis-menu__trigger collapsible-dropdown__button btn-md btn-tertiary cursor-pointer !py-[6px] !px-1 flex items-center rounded-[50%] " aria-expanded="false" aria-label="Open menu" data-tracking-control-name="public_post_ellipsis-menu-trigger" tabindex="0"> <icon class="ellipsis-menu__trigger-icon m-0 p-0 centered-icon" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/671xosfpvk4c0kqtyl87hashi"></icon> </button> <ul class="collapsible-dropdown__list hidden container-raised absolute w-auto overflow-y-auto flex-col items-stretch z-1 bottom-auto top-[100%]" role="menu" tabindex="-1"> <li class="ellipsis-menu__item border-t-1 border-solid border-color-border-low-emphasis first-of-type:border-none flex"> <a href="/uas/login?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Fposts%2Fpieter-de-richter-82b9853_mechanistic-patterns-and-clinical-implications-activity-7210855135864836097-lBRR&trk=public_post_ellipsis-menu-semaphore-sign-in-redirect&guestReportContentType=POST&_f=guest-reporting" data-tracking-control-name="public_post_ellipsis-menu-semaphore-sign-in-redirect" data-tracking-will-navigate data-item-type="semaphore" data-semaphore-content-type="POST" data-semaphore-content-urn="urn:li:activity:7210855135864836097" data-semaphore-tracking-prefix="public_post_ellipsis-menu-semaphore" data-is-logged-in="false" data-modal="semaphore__toggle" class="semaphore__toggle visited:text-color-text-secondary ellipsis-menu__semaphore ellipsis-menu__item-button flex items-center w-full p-1 cursor-pointer font-sans text-sm font-bold link-styled focus:link-styled link:no-underline active:bg-color-background-container-tint focus:bg-color-background-container-tint hover:bg-color-background-container-tint outline-offset-[-2px]">  <icon class="ellipsis-menu__item-icon text-color-text h-[24px] w-[24px] mr-1" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/iq0x9q37wj214o129ai1yjut"> </icon> Report this post </a>  </li>  </ul>  </div> </div> </div> <div class="attributed-text-segment-list__container relative mt-1 mb-1.5 babybear:mt-0 babybear:mb-0.5"> <p class="attributed-text-segment-list__content text-color-text !text-sm whitespace-pre-wrap break-words " dir="ltr" data-test-id="main-feed-activity-card__commentary">Very interesting study. We're used to talking about EML4-ALK fusions, CD74-ROS1 fusions, KIF5B-RET fusions etc... but why don't we see e.g. EML4-ROS1 or CD74-ALK fusions? Active transcription of the partner genes and protein stability of the fusion products play key roles. </p>  </div> <article aria-label="Reshared post" class="relative pt-1.5 px-2 pb-1 mb-1 babybear:pt-0.5 babybear:pb-0 babybear:mb-0 container-lined bg-color-background-container feed-reshare-content" data-test-id="feed-reshare-content" data-attributed-urn="urn:li:share:7209911303950270466" data-activity-urn="urn:li:activity:7209911304600367104" tabindex="0"> <div class="flex items-center font-sans" data-test-id="feed-reshare-content__entity-lockup"> <a href="https://www.linkedin.com/in/biagio-ricciuti-0519a097?trk=public_post_reshare_feed-actor-image" target="_self" class="relative" data-tracking-control-name="public_post_reshare_feed-actor-image" data-tracking-will-navigate> <img class="inline-block relative rounded-[50%] w-6 h-6 " data-delayed-url="https://media.licdn.com/dms/image/v2/D5603AQHvxVUZ53rK6Q/profile-displayphoto-shrink_400_400/profile-displayphoto-shrink_400_400/0/1642539900958?e=2147483647&v=beta&t=-VFEa0RXpJ7M67Wy11ZrCnJz0y_SFFHiYZg3w2Hez6k" data-ghost-classes="bg-color-entity-ghost-background" data-ghost-url="https://static.licdn.com/aero-v1/sc/h/9c8pery4andzj6ohjkjp54ma2" alt="View profile for Biagio Ricciuti, graphic">  </a> <div class="flex flex-col self-start min-w-0 ml-1 "> <div class="text-color-text "> <a class="text-sm link-styled no-underline leading-open" href="https://www.linkedin.com/in/biagio-ricciuti-0519a097?trk=public_post_reshare_feed-actor-name" target="_self" data-tracking-control-name="public_post_reshare_feed-actor-name" aria-label="View profile for Biagio Ricciuti" data-tracking-will-navigate> Biagio Ricciuti </a>  </div> <p class="!text-xs text-color-text-low-emphasis leading-[1.33333] m-0 truncate">  Medical Oncologist </p> <span class="!text-xs text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 5mo <span aria-hidden="true" class="text-color-text-low-emphasis before:middot"></span> <span> Edited </span> </time>  </span> </div>  </div> <div class="attributed-text-segment-list__container relative mt-1 mb-1.5 babybear:mt-0 babybear:mb-0.5"> <p class="attributed-text-segment-list__content text-color-text !text-sm whitespace-pre-wrap break-words " dir="ltr" data-test-id="feed-reshare-content__commentary">Fusion partners and chromosomal breakpoints of oncogenic fusions involving <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Falk&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#ALK</a>, <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fros1&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#ROS1</a>, <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fret&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#RET</a> and <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fntrk1&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#NTRK1</a> are not random! In study out in <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fnaturecommunications&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#NatureCommunications</a> we demonstrate that <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Ftypical&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#typical</a> kinase domain fusions are selected from pools of chromosomal rearrangements by 2 major determinants including: 1. Active transcription of the fusion partner genes 2. Protein stability In contrast, <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fatypical&trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>#atypical</a> TK fusions that are rarely seen in patients showed reduced protein stability, decreased downstream oncogenic signaling, and were less responsive to inhibition. <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FeRydBV_f&urlhash=2EAS&trk=public_post_reshare-text" target="_self" rel="nofollow" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>https://lnkd.in/eRydBV_f</a> <a class="link" href="https://www.linkedin.com/company/bostonchildrenshospital?trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>Boston Children's Hospital</a> and <a class="link" href="https://www.linkedin.com/company/dana-farber-cancer-institute?trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>Dana-Farber Cancer Institute</a> <a class="link" href="https://www.linkedin.com/school/harvard-medical-school/?trk=public_post_reshare-text" target="_self" data-tracking-control-name="public_post_reshare-text" data-tracking-will-navigate>Harvard Medical School</a></p>  </div>  <a href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Fpubmed%2Encbi%2Enlm%2Enih%2Egov%2F38877018%2F&urlhash=gQgY&trk=public_post_reshare_feed-article-content" target="_self" data-tracking-control-name="public_post_reshare_feed-article-content" data-tracking-will-navigate class="flex flex-col feed-article-content" data-test-id="article-content"> <img alt="Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers - PubMed" class="lazy-load 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To address this, researchers have turned to β-cyclodextrins (β-CD) complexes, aiming to overcome limitations posed by compounds like p-Cymene (PC), known for its antinociceptive effects but hampered by its lipophilicity. This study focused on obtaining, characterizing, and assessing the impact of the p-cymene and β-cyclodextrin (PC/β-CD) complex in a cancer pain model. For a deeper insight, click on the link and read <a class="link" href="https://hu.linkedin.com/in/eva-fenyvesi-34417b14?trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>Eva Fenyvesi</a>'s blog post on Cyclodextrin News: <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FdiwCYsEP&urlhash=GDc6&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/diwCYsEP</a> <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fcyclolab&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#cyclolab</a> <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fcyclodextrin&trk=public_post-text" target="_self" 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Cross-Functional Collaborator | Lead Optimization | Waterfall | R&D | Cricket | Vedic Astrology | </p> <span class="!text-xs text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 9mo  </time>  </span> </div>  </div> </div> <div class="ellipsis-menu absolute right-0 top-0 main-feed-activity-card__ellipsis-menu !top-auto !relative !mr-1" data-test-id="main-feed-activity-card__ellipsis-menu"> <div class="collapsible-dropdown flex items-center relative hyphens-auto"> <button class="ellipsis-menu__trigger collapsible-dropdown__button btn-md btn-tertiary cursor-pointer !py-[6px] !px-1 flex items-center rounded-[50%] " aria-expanded="false" aria-label="Open menu" data-tracking-control-name="public_post_ellipsis-menu-trigger" tabindex="0"> <icon class="ellipsis-menu__trigger-icon m-0 p-0 centered-icon" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/671xosfpvk4c0kqtyl87hashi"></icon> </button> <ul class="collapsible-dropdown__list hidden container-raised 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data-tracking-will-navigate>https://lnkd.in/gYdrCZh6</a> The RAS protein plays a pivotal role in cellular proliferation and differentiation, with mutations driving oncogenic alterations in cancer. Despite being classified as undruggable, recent advances have identified covalent binders targeting the mutated cysteine residue (G12C) of KRAS protein as effective for solid tumor treatment. We present a series of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as potent covalent inhibitors against KRAS G12C, optimized through structural modifications of the acryloyl amine moiety. Structural analysis revealed binding of the moiety in the switch-II pocket of KRAS G12C. Further optimization yielded compound 7b, exhibiting high metabolic stability and dose-dependent antitumor effects in an NCI-H1373 xenograft mouse model upon subcutaneous administration.</p>  </div> <ul class="grid grid-cols-6 grid-rows-[60%_40%] w-main-feed-card-media feed-images-content list-none pl-0 " data-test-id="feed-images-content"> <li class="bg-color-background-container-tint text-[0px] col-span-full row-span-full " data-test-id="feed-images-content__list-item" data-position="0"> <img class="lazy-load w-full object-cover object-center h-full babybear:max-h-[400px]" data-delayed-url="https://media.licdn.com/dms/image/v2/D5622AQHE9EMZyqj2qA/feedshare-shrink_800/feedshare-shrink_800/0/1707165521935?e=2147483647&v=beta&t=0vLgvH9a9cM5dMwDuuJhoslxwXY0Djg9-1uoJpiXZAQ" data-ghost-url="https://static.licdn.com/aero-v1/sc/h/921ynb2z53z33mhm3061qvjag" alt="No alternative text description for this image">  </li> </ul>  <code id="i18n_reaction_singular" style="display: none"></code> <code 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border-color-surface-border border-solid p-3 text-center text-md text-color-text-low-emphasis"> To view or add a comment, <a href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Fposts%2Fgajanansinamdar_httpslnkdingydrczh6-the-ras-protein-activity-7160371183064932352-45Yg&trk=public_post_feed-cta-banner-cta" target="" aria-label="To view or add a comment, sign in" data-tracking-control-name="public_post_feed-cta-banner-cta" data-tracking-will-navigate="true" class="feed-cta-banner__link link">sign in</a> </p> </article> <code id="is-mobile" style="display: none"></code> </div> </li> <li class="mb-1.5"> <div class="link-overlay relative"> <a aria-label="Post by Hans Lennernäs" class="absolute left-0 top-0 h-full w-full z-1 !border-0" data-tracking-control-name="link-overlay-public_post" href="https://www.linkedin.com/posts/hans-lennern%C3%A4s-2369452a_coinhibition-of-topoisomerase-1-and-brd4-activity-7174868995173453824-rKA9" target="_self"></a> <article class="relative px-2 pb-0 bg-color-background-container container-lined pt-1.5 main-feed-activity-card related-posts__crosslink" data-activity-urn="urn:li:activity:7174868995173453824" data-featured-activity-urn="urn:li:activity:7174868995173453824" data-attributed-urn="urn:li:share:7174868994628141057">   <div class="flex"> <div class="base-main-feed-card__entity-lockup"> <div class="flex items-center font-sans mb-1" data-test-id="main-feed-activity-card__entity-lockup"> <a href="https://se.linkedin.com/in/hans-lennern%C3%A4s-2369452a?trk=public_post_feed-actor-image" class="relative" data-tracking-control-name="public_post_feed-actor-image" data-tracking-will-navigate> <img class="inline-block relative rounded-[50%] w-6 h-6 " data-delayed-url="https://media.licdn.com/dms/image/v2/C4E03AQG4I8sylImJhg/profile-displayphoto-shrink_400_400/profile-displayphoto-shrink_400_400/0/1540568094544?e=2147483647&v=beta&t=8RyZGIZQ5_Gduma6W__WIMbqk7AYfTrsYOztu-oL7NE" 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href="/uas/login?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Fposts%2Fhans-lennern%25C3%25A4s-2369452a_coinhibition-of-topoisomerase-1-and-brd4-activity-7174868995173453824-rKA9&trk=public_post_ellipsis-menu-semaphore-sign-in-redirect&guestReportContentType=POST&_f=guest-reporting" data-tracking-control-name="public_post_ellipsis-menu-semaphore-sign-in-redirect" data-tracking-will-navigate data-item-type="semaphore" data-semaphore-content-type="POST" data-semaphore-content-urn="urn:li:activity:7174868995173453824" data-semaphore-tracking-prefix="public_post_ellipsis-menu-semaphore" data-is-logged-in="false" data-modal="semaphore__toggle" class="semaphore__toggle visited:text-color-text-secondary ellipsis-menu__semaphore ellipsis-menu__item-button flex items-center w-full p-1 cursor-pointer font-sans text-sm font-bold link-styled focus:link-styled link:no-underline active:bg-color-background-container-tint focus:bg-color-background-container-tint hover:bg-color-background-container-tint outline-offset-[-2px]">  <icon class="ellipsis-menu__item-icon text-color-text h-[24px] w-[24px] mr-1" data-delayed-url="https://static.licdn.com/aero-v1/sc/h/iq0x9q37wj214o129ai1yjut"> </icon> Report this post </a>  </li>  </ul>  </div> </div> </div> <div class="attributed-text-segment-list__container relative mt-1 mb-1.5 babybear:mt-0 babybear:mb-0.5"> <p class="attributed-text-segment-list__content text-color-text !text-sm whitespace-pre-wrap break-words " dir="ltr" data-test-id="main-feed-activity-card__commentary">Coinhibition of topoisomerase 1 (TOP1) and bromodomain-containing protein 4 (BRD4) synergistically induces tumor regression. This synergistic effect of TOP1 + BRD4 inhibition is specific to cancer cells leaving normal cells unaffected, which is very interesting from safety and quality-of-life perspective. We have a strong interest from our research on chemotherapy induced mucositis. <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FdMweZ2QU&urlhash=Id9E&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/dMweZ2QU</a> </p>  </div>  <a href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Fpubmed%2Encbi%2Enlm%2Enih%2Egov%2F37831776%2F&urlhash=Gnpv&trk=public_post_feed-article-content" target="_self" data-tracking-control-name="public_post_feed-article-content" data-tracking-will-navigate class="flex flex-col feed-article-content" data-test-id="article-content"> <img alt="Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription - PubMed" class="lazy-load w-main-feed-card-media object-cover babybear:max-h-[400px]" 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href="https://www.linkedin.com/posts/biagio-ricciuti-0519a097_mechanistic-patterns-and-clinical-implications-activity-7209911304600367104-JRdN" target="_self"></a> <article class="relative px-2 pb-0 bg-color-background-container container-lined pt-1.5 main-feed-activity-card related-posts__crosslink" data-activity-urn="urn:li:activity:7209911304600367104" data-featured-activity-urn="urn:li:activity:7209911304600367104" data-attributed-urn="urn:li:share:7209911303950270466">   <div class="flex"> <div class="base-main-feed-card__entity-lockup"> <div class="flex items-center font-sans mb-1" data-test-id="main-feed-activity-card__entity-lockup"> <a href="https://www.linkedin.com/in/biagio-ricciuti-0519a097?trk=public_post_feed-actor-image" class="relative" data-tracking-control-name="public_post_feed-actor-image" data-tracking-will-navigate> <img class="inline-block relative rounded-[50%] w-6 h-6 " 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In study out in <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fnaturecommunications&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#NatureCommunications</a> we demonstrate that <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Ftypical&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#typical</a> kinase domain fusions are selected from pools of chromosomal rearrangements by 2 major determinants including: 1. Active transcription of the fusion partner genes 2. Protein stability In contrast, <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fatypical&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#atypical</a> TK fusions that are rarely seen in patients showed reduced protein stability, decreased downstream oncogenic signaling, and were less responsive to inhibition. <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FeRydBV_f&urlhash=2EAS&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/eRydBV_f</a> <a class="link" href="https://www.linkedin.com/company/bostonchildrenshospital?trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>Boston Children's Hospital</a> and <a class="link" 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HNSCCs are characterized by altered levels of angiogenesis-related factors, including the overexpression of pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), as well as the dysregulation of angiogenesis inhibitors. Together, these factors drive the formation of new blood vessels within the tumor microenvironment and are considered therapeutic targets in HNSCC. Although preclinical studies are promising, challenges have emerged in the clinical use of anti-angiogenic agents in the clinic, including treatment-related toxicities and the development of resistance to therapy. There is an unmet need for further research to elucidate the molecular pathways involved in HNSCC angiogenesis, identify novel therapeutic targets, and discover predictive biomarkers to improve patient selection.“ 📕 Read more: <a class="link" href="https://www.linkedin.com/redir/redirect?url=https%3A%2F%2Flnkd%2Ein%2FgumUVDy4&urlhash=78oX&trk=public_post-text" target="_self" rel="nofollow" data-tracking-control-name="public_post-text" data-tracking-will-navigate>https://lnkd.in/gumUVDy4</a> Authors: Felix Nieberle, Steffen Spoerl, Alicja Głuszko, Juergen Taxis, Gerrit Spanier, Ramona Erber, Silvia Spoerl, Mirosław J. Szczepański, Philipp Beckhove, Torsten E. Reichert, Theresa L. 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href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Fposts%2Fnicole-an-817012239_abstract-angiogenesis-the-formation-activity-7214202367834013697-_-Jo&trk=public_post_feed-cta-banner-cta" target="" aria-label="To view or add a comment, sign in" data-tracking-control-name="public_post_feed-cta-banner-cta" data-tracking-will-navigate="true" class="feed-cta-banner__link link">sign in</a> </p> </article> <code id="is-mobile" style="display: none"></code> </div> </li> <li class="mb-1.5"> <div class="link-overlay relative"> <a aria-label="Post by Himanshu Mishra" class="absolute left-0 top-0 h-full w-full z-1 !border-0" data-tracking-control-name="link-overlay-public_post" href="https://www.linkedin.com/posts/himanshu-mishra-299105173_mswi-highlights-activity-7221315393024360448-DKDU" target="_self"></a> <article class="relative px-2 pb-0 bg-color-background-container container-lined pt-1.5 main-feed-activity-card related-posts__crosslink" data-activity-urn="urn:li:activity:7221315393024360448" data-featured-activity-urn="urn:li:activity:7221315393024360448" data-attributed-urn="urn:li:share:7221315389899587584">   <div class="flex"> <div class="base-main-feed-card__entity-lockup"> <div class="flex items-center font-sans mb-1" data-test-id="main-feed-activity-card__entity-lockup"> <a href="https://in.linkedin.com/in/himanshu-mishra-299105173?trk=public_post_feed-actor-image" class="relative" data-tracking-control-name="public_post_feed-actor-image" data-tracking-will-navigate> <img class="inline-block relative rounded-[50%] w-6 h-6 " data-delayed-url="https://media.licdn.com/dms/image/v2/D4D03AQGbPGOJvkS3GQ/profile-displayphoto-shrink_400_400/profile-displayphoto-shrink_400_400/0/1726232434570?e=2147483647&v=beta&t=vgdc-BDeQPdoiglyL8HFt4QIQKQmKGI5DLCFB4zm4g8" data-ghost-classes="bg-color-entity-ghost-background" data-ghost-url="https://static.licdn.com/aero-v1/sc/h/9c8pery4andzj6ohjkjp54ma2" alt="View profile for Himanshu Mishra, graphic">  </a> <div class="flex flex-col self-start min-w-0 ml-1 "> <div class="text-color-text "> <a class="text-sm link-styled no-underline leading-open" href="https://in.linkedin.com/in/himanshu-mishra-299105173?trk=public_post_feed-actor-name" data-tracking-control-name="public_post_feed-actor-name" aria-label="View profile for Himanshu Mishra" data-tracking-will-navigate> Himanshu Mishra </a>  </div> <p class="!text-xs text-color-text-low-emphasis leading-[1.33333] m-0 truncate">  Microbiologist At Zydus Lifescience pvt Ltd Ahemdabad </p> <span class="!text-xs text-color-text-low-emphasis leading-[1.33333] flex"> <time class="flex-none"> 4mo  </time>  </span> </div>  </div> </div> <div class="ellipsis-menu absolute right-0 top-0 main-feed-activity-card__ellipsis-menu !top-auto !relative !mr-1" data-test-id="main-feed-activity-card__ellipsis-menu"> <div class="collapsible-dropdown flex items-center relative hyphens-auto"> <button class="ellipsis-menu__trigger 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class="attributed-text-segment-list__container relative mt-1 mb-1.5 babybear:mt-0 babybear:mb-0.5"> <p class="attributed-text-segment-list__content text-color-text !text-sm whitespace-pre-wrap break-words " dir="ltr" data-test-id="main-feed-activity-card__commentary">Targeting the <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fmswi&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#mSWI</a>/SNF complex in POU2F-POU2AF transcription factor-driven malignancies:- •The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). •Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. •Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. •B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. •An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. •This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability. <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Fhighlights&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#highlights</a>:- •mSWI/SNF complex and its ATPase subunit are epigenetic dependencies in SCLC-P. •POU2F3 complex requires the mSWI/SNF complex to modulate chromatin accessibility. •POU2AF1 and IRF4 function as an epigenetic complex requiring mSWI/SNF in MM. •An oral mSWI/SNF ATPase degrader shows potent anti-tumor efficacy in SCLC-P and MM.</p>  </div> <ul class="grid grid-cols-6 grid-rows-[60%_40%] w-main-feed-card-media feed-images-content list-none pl-0 " data-test-id="feed-images-content"> <li class="bg-color-background-container-tint text-[0px] col-span-full row-span-full " data-test-id="feed-images-content__list-item" data-position="0"> <img class="lazy-load w-full object-cover object-center h-full babybear:max-h-[400px]" data-delayed-url="https://media.licdn.com/dms/image/v2/D4D22AQGvj2mvRbhi_g/feedshare-shrink_2048_1536/feedshare-shrink_2048_1536/0/1721695752890?e=2147483647&v=beta&t=CB6hf1iVqWunfwl0s5mRJArKmwW_XI5UPEVkXEW7hGw" data-ghost-url="https://static.licdn.com/aero-v1/sc/h/921ynb2z53z33mhm3061qvjag" 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Innovative strategies like new-generation CARs and combination therapies are emerging. Tumor <a class="link" href="https://www.linkedin.com/signup/cold-join?session_redirect=https%3A%2F%2Fwww.linkedin.com%2Ffeed%2Fhashtag%2Forganoids&trk=public_post-text" target="_self" data-tracking-control-name="public_post-text" data-tracking-will-navigate>#organoids</a>, particularly patient-derived ones, offer accurate models for testing CAR T-cells. 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Nanodigmbio Biotechnology on LinkedIn: Prediction of homologous recombination deficiency identifies colorectal…