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Permanent URI for this collectionhttps://hdl.handle.net/11443/932

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Author: search.filters.author.Dogruoez, Alper

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    Molecular Profiling in Pancreatic Cancer: Current Role and Its Impact on Primary Surgery
    (KARGER, 2019-01-01) Mota Reyes, Carmen; Dogruoez, Alper; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Gueralp O.; Demir, Ihsan Ekin
    Background: The advent of next-generation sequencing technologies has enabled the identification of molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) with different biological traits and clinically targetable features. Summary: Although current chemotherapy trials are currently exploiting this knowledge, these molecular subtypes have not yet sufficiently caught the attention of surgeons. In fact, integration of these molecular subtypes into the timing of surgery can in theory improve patient outcome. Here, we present the molecular subtypes of PDAC from the surgeon's perspective and a clinically applicable algorithm that integrates the molecular subtyping of PDAC preoperatively into the decision of primary surgery versus neoadjuvant therapy. Furthermore, we point out the potential of ``tailored{''} (in addition to conventional) neoadjuvant treatment for exploiting the molecular subtypes of PDAC. Key Messages: We believe that for surgeons, the preoperative knowledge on the subtype of PDAC can properly guide in deciding between upfront surgery versus neoadjuvant treatment for improving patient outcome.
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    Targeting the undruggable oncogenic KRAS: the dawn of hope
    (AMER SOC CLINICAL INVESTIGATION INC, 2022-01-01) Asimgil, Hande; Ertetik, Utku; Cevik, Nedim Can; Ekizce, Menar; Dogruoez, Alper; Goekalp, Muazzez; Arik-Sever, Elif; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Guralp Onur; Demir, Ihsan Ekin
    KRAS mutations are the drivers of various cancers, including non-small cell lung cancer, colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been made to inhibit KRAS mutants and oncogenic KRAS signaling using inhibitors. Recently, specific targeting of KRAS mutants with small molecules revived the hopes for successful therapies for lung, pancreatic, and colorectal cancer patients. Moreover, advances in gene editing, protein engineering, and drug delivery formulations have revolutionized cancer therapy regimens. New therapies aim to improve immune surveillance and enhance antitumor immunity by precisely targeting cancer cells harboring oncogenic KRAS. Here, we review recent KRAS-targeting strategies, their therapeutic potential, and remaining challenges to overcome. We also highlight the potential synergistic effects of various combinatorial therapies in preclinical and clinical trials.