Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications

Author:

Gouda Mohamed A.1ORCID,Nelson Blessie E.1ORCID,Buschhorn Lars2ORCID,Wahida Adam2ORCID,Subbiah Vivek134ORCID

Affiliation:

1. 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

2. 2Division of Gynecological Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany.

3. 3Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

4. 4MD Anderson Cancer Network, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

Abstract Biomarker-driven cancer therapy has revolutionized precision oncology. With a better understanding of tumor biology, tissue-agnostic targets have been characterized and explored, which ultimately led to therapeutics with pan-cancer efficacy. To date, five molecular biomarkers have obtained FDA tissue-agnostic approval for targeted therapies and immunotherapies. Those include BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and deficient mismatch repair/high microsatellite instability (dMMR/MSI-High). Herein, we have used data from AACR project GENIE to explore the clinico-genomic landscape of these alterations. AACR GENIE is a publicly accessible registry of genomic data from multiple collaborating cancer centers. Current database (version 13.0) includes sequencing data of 168,423 samples collected from patients with different cancers. We were able to identify BRAFV600E, RET fusions, NTRK fusions, and high TMB in 2.9%, 1.6%, 1.5%, and 15.2% of pan-cancer samples, respectively. In this article, we describe the distribution of those tissue-agnostic targets among different cancer types. In addition, we summarize the current prospect on the biology of these alterations and evidence on approved drugs, including pembrolizumab, dostarilmab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combination.

Funder

Cancer Prevention and Research Institute of Texas

National Center for Advancing Translational Sciences

National Institutes of Health

Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3