Shiuh-Wen Luoh, MD, PhD; Keith T. Flaherty, MD
Disclosures: Dr. Luoh serves as a consultant to Amgen outside the submitted work. Dr. Flaherty is on the Board of Directors for Loxo Oncology and serves as a consultant to Loxo Oncology, Debiopharm, and Merck. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2832.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Corresponding Author: Shiuh-Wen Luoh, MD, PhD, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, R&D 47, Portland, OR 97239; e-mail, luohs@OHSU.edu.
Current Author Addresses: Dr. Luoh: VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, R&D 47, Portland, OR 97239.
Dr. Flaherty: Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114.
Author Contributions: Conception and design: S.W. Luoh, K.T. Flaherty.
Analysis and interpretation of the data: S.W. Luoh, K.T. Flaherty.
Drafting of the article: S.W. Luoh, K.T. Flaherty.
Critical revision of the article for important intellectual content: S.W. Luoh, K.T. Flaherty.
Final approval of the article: S.W. Luoh, K.T. Flaherty.
Administrative, technical, or logistic support: S.W. Luoh, K.T. Flaherty.
Collection and assembly of data: S.W. Luoh.
Matching unique features of cancer types with effective therapies is a cornerstone of precision medicine. Clinical success has been seen in inhibiting specific molecular alterations that drive the growth of cancer cells and targeting molecules whose elevated expression is confined to cancer cells. In addition, cancer cells can have vulnerabilities induced by somatic mutations they carry; attacks on these vulnerabilities range from specific molecular alterations pointing to direct drug strategies to harnessing immune recognition of genetically altered epitopes produced by the cancer cells. Recent advances have found that the success of biomarker-driven cancer therapy may be relevant across sites of origin. For example, cancer types that show DNA mismatch repair deficiency, such as colon, biliary, and endometrial cancer, are more sensitive to immune checkpoint inhibition. Several large, ongoing clinical trials with a “basket” design are combining tumor tissue genomics with potential off-the-shelf therapies in drug development, and more tissue-agnostic biomarker therapies are reaching the bedside.
Luoh S, Flaherty KT. When Tissue Is No Longer the Issue: Tissue-Agnostic Cancer Therapy Comes of Age. Ann Intern Med. 2018;169:233–239. [Epub ahead of print 24 July 2018]. doi: 10.7326/M17-2832
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Published: Ann Intern Med. 2018;169(4):233-239.
Published at www.annals.org on 24 July 2018
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