Understanding Drug Sensitivity and Tackling Resistance in Cancer

Author:

Tyner Jeffrey W.12ORCID,Haderk Franziska345,Kumaraswamy Anbarasu6ORCID,Baughn Linda B.7,Van Ness Brian8,Liu Song9,Marathe Himangi9,Alumkal Joshi J.6ORCID,Bivona Trever G.345,Chan Keith Syson1011,Druker Brian J.12ORCID,Hutson Alan D.9ORCID,Nelson Peter S.1213ORCID,Sawyers Charles L.1415ORCID,Willey Christopher D.16ORCID

Affiliation:

1. Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

2. Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, Oregon.

3. Department of Medicine, University of California, San Francisco, San Francisco, California.

4. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

5. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California.

6. Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.

7. Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

8. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota.

9. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

10. Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.

11. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

12. Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington.

13. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.

14. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, New York.

15. Howard Hughes Medical Institute, Chevy Chase, Maryland.

16. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

AbstractDecades of research into the molecular mechanisms of cancer and the development of novel therapeutics have yielded a number of remarkable successes. However, our ability to broadly assign effective, rationally targeted therapies in a personalized manner remains elusive for many patients, and drug resistance persists as a major problem. This is in part due to the well-documented heterogeneity of cancer, including the diversity of tumor cell lineages and cell states, the spectrum of somatic mutations, the complexity of microenvironments, and immune-suppressive features and immune repertoires, which collectively require numerous different therapeutic approaches. Here, we describe a framework to understand the types and biological causes of resistance, providing translational opportunities to tackle drug resistance by rational therapeutic strategies.

Funder

NCI

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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