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Li et al. J Cancer Metastasis Treat 2020;6:14 Journal of Cancer
DOI: 10.20517/2394-4722.2020.27 Metastasis and Treatment

Review Open Access

Opportunities and challenges in developing tissue-
agnostic anti-cancer drugs

Ivan W. Li , Nithya Krishnamurthy , Ge Wei , Gary Li 3,4
1
2
3,4
1 Current affiliation: Canyon Crest Academy, San Diego, CA 92130, USA.
2 Current affiliation: Yale University, New Haven, CT 06520, USA.
3 Translational Research, Ignyta, Inc., San Diego, CA 92121, USA.
4 Current affiliation: Translational Medicine, QED Therapeutics, San Francisco, CA 94107, USA.
Correspondence to: Dr. Gary Li, Translational Medicine, QED Therapeutics, 75 Federal Street, San Francisco, CA 94107, USA.
E-mail: garyli1210@yahoo.com

How to cite this article: Li IW, Krishnamurthy N, Wei G, Li G. Opportunities and challenges in developing tissue-agnostic anti-
cancer drugs. J Cancer Metastasis Treat 2020;6:14. http://dx.doi.org/ 10.20517/2394-4722.2020.27

Received: 31 Mar 2020 First Decision: 29 Apr 2020 Revised: 2 May 2020 Accepted: 18 May 2020 Published: 27 May 2020
Science Editor: Godefridus J. Peters Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
The rapid advances in the understanding of oncogenic process and the maturation of affordable precision
diagnostic tools have enabled the development of targeted therapeutic agents, such as those targeting BCR-
ABL, epithelial growth factor receptor L858R, EML4-anaplastic lymphoma kinase, and BRAF V600E, to treat
cancers that harbor specific molecular alterations. Traditionally, each targeted drug has been developed for a
particular tumor type where such alteration is most frequently found. Recently, the widespread adoption of next
generation sequencing has led to an increase in the identification of rare and ultra-rare alterations, and, in some
cases, the same rare alterations are found across multiple tumor types. The rarity of these alterations makes
clinical trials traditionally designed for specific tumor types infeasible. As a result, tissue-agnostic trials have been
developed to study the efficacy of these treatments and increase patient access. This review summarizes current
successful cases of tissue-agnostic development, such as drugs targeting tropomyosin receptor kinase fusions,
and proposes the next wave of potential tissue-agnostic targets, including fusions of ROS1, anaplastic lymphoma
kinase, fibroblast growth factor receptor, and rearranged during transfection. In addition, the advantages and the
challenges of such approach are discussed in the context of clinical development and approval.

Keywords: Tissue agnostic, basket trial, tropomyosin receptor kinase, anaplastic lymphoma kinase, ROS1, fibroblast
growth factor receptor, rearranged during transfection

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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