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Precision medicine for gastrointestinal cancers: a conference report.

ABSTRACT: As cancer management evolves into precision medicine national/international cancer meetings bring novel therapeutic approaches and potentially practice-changing results of clinical studies are presented. This year, the ASCO GI Symposium 2020 had also several updates from ongoing and finalized clinical trials. Although there were no groundbreaking results that impact the daily practice directly, several highly important data from ongoing studies were shared with the audience. In this report, the highlights of the ASCO GI Symposium 2020 are presented with a future perspective.

SUBMITTER: Sahin IH

PROVIDER: S-EPMC7351088 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Precision medicine for gastrointestinal cancers: a conference report.

Sahin Ibrahim Halil IH

Future science OA 20200527 6

As cancer management evolves into precision medicine national/international cancer meetings bring novel therapeutic approaches and potentially practice-changing results of clinical studies are presented. This year, the ASCO GI Symposium 2020 had also several updates from ongoing and finalized clinical trials. Although there were no groundbreaking results that impact the daily practice directly, several highly important data from ongoing studies were shared with the audience. In this report, the ...[more]

PMID: 32670606

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Project description:NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. Notch signaling is aberrantly activated in breast cancer, non‑small‑cell lung cancer and hematological malignancies, such as T‑cell acute lymphoblastic leukemia and diffuse large B‑cell lymphoma. However, Notch signaling is inactivated in small‑cell lung cancer and squamous cell carcinomas. Loss‑of‑function NOTCH1 mutations are early events during esophageal tumorigenesis, whereas gain‑of‑function NOTCH1 mutations are late events during T‑cell leukemogenesis and B‑cell lymphomagenesis. Notch signaling cascades crosstalk with fibroblast growth factor and WNT signaling cascades in the tumor microenvironment to maintain cancer stem cells and remodel the tumor microenvironment. The Notch signaling network exerts oncogenic and tumor‑suppressive effects in a cancer stage‑ or (sub)type‑dependent manner. Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. The DLL3‑targeting antibody‑drug conjugate (ADC) Rova‑T, and DLL3‑targeting chimeric antigen receptor‑modified T cells (CAR‑Ts), AMG 119, are promising anti‑cancer therapeutics, as are other ADCs or CAR‑Ts targeting tumor necrosis factor receptor superfamily member 17, CD19, CD22, CD30, CD79B, CD205, Claudin 18.2, fibroblast growth factor receptor (FGFR)2, FGFR3, receptor‑type tyrosine‑protein kinase FLT3, HER2, hepatocyte growth factor receptor, NECTIN4, inactive tyrosine‑protein kinase 7, inactive tyrosine‑protein kinase transmembrane receptor ROR1 and tumor‑associated calcium signal transducer 2. ADCs and CAR‑Ts could alter the therapeutic framework for refractory cancers, especially diffuse‑type gastric cancer, ovarian cancer and pancreatic cancer with peritoneal dissemination. Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. Integration of human intelligence, cognitive computing and explainable artificial intelligence is necessary to construct a Notch‑related knowledge‑base and optimize Notch‑targeted therapy for patients with cancer.

Dataset Information

Precision medicine for gastrointestinal cancers: a conference report.

Publications

Precision medicine for gastrointestinal cancers: a conference report.

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