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Develop Ways to Overcome Cancer’s Resistance to Therapy

NCI has announced several funding opportunities that align with the Cancer Moonshot.

See Funding Opportunities

Cancer cells may develop the ability to rewire or reprogram themselves to become resistant to treatments that were previously effective. Drug resistance accounts for many cancer recurrences and associated deaths. Despite progress in understanding drug resistance over the last decade, knowledge gaps remain about the underlying biological causes of drug resistance and the design of cancer treatments to overcome it.

This recommendation aims to address these gaps through an interdisciplinary effort to determine targets for the development of new cancer treatments that prevent or overcome drug resistance. Research teams involved in this initiative will use new experimental models to comprehensively characterize sensitivities of drug resistant cancer cells using clinical samples taken before, during, and after treatment. In addition, the research teams will work to better understand the pathways and mechanisms that allow tumors to become resistant to a given treatment.

This national collaborative research will include both pediatric and adult tumor types and representation from minority and underserved populations, as each population may have resistance mechanisms that are unique.

Ultimately, the hope is that knowledge gained from this initiative will be used to develop more effective therapies—tailored to an individual’s condition—to overcome treatment resistance, as well as to identify biomarker signatures that will guide different cancer treatment options to prevent the development of drug resistance.

NCI has awarded funding to several research projects that align with this recommendation’s goal to overcome drug resistance:

Drug Resistance and Sensitivity Network

NCI has created a network of drug resistance and sensitivity research centers, which is developing new experimental models for studying drug resistance in tumors, investigate mechanisms of drug resistance in cancer, and design innovative approaches to exploit the sensitivity of cancer cells to specific treatments. This consortium includes teams of cancer biologists, computational scientists, clinicians, and model developers who are performing “bench and bedside” translational studies of cancer drug resistance and sensitivity. Along with research contributions, the network is also building a collection of resources that can be used by the cancer researchers examining mechanisms of drug resistance. The findings and models from this multidisciplinary network will inform the design of new clinical cancer treatments that can prevent or overcome drug resistance to anti-cancer therapies.

The drug resistance and sensitivity network is also involved in collaborative studies with investigators outside of the research consortium. These cooperative projects expand the network’s reach and promote data and resource sharing for understanding cancer drug resistance. The results from these collaborative, experimental studies will support the development of new cancer treatment strategies.

MasterLymph: A Precision Medicine Protocol to Improve Therapy of Relapsed/Refractory Diffuse Large B Cell Lymphoma

One type of cancer with multiple mechanisms of drug resistance is Diffuse Large B Cell Lymphoma (DLBCL). Many clinical trials testing a single drug to treat DLBCL have been unsuccessful due to the development of drug resistance. To overcome these challenges, NCI researchers, in collaboration with cancer centers, are testing combinations of targeted treatments in MasterLymph. In this clinical trial, researchers are measuring biomarkers in patients to predict individual responses to specific drugs. This information is used to identify effective drug combinations that can treat lymphoma and overcome drug resistance.

Drug Resistance Projects Awarded Cancer Moonshot Funding

Awarded Projects
Funding Opportunity Project Title Institution Principal Investigator(s)

Drug Resistance and Sensitivity/Research to Identify and Treat Cancer Sensitivity or Resistance to Anticancer Therapy (U54)

Overcoming Drug Resistance in Multiple Myeloma

Mayo Clinic Arizona

Stewart, Alexander Keith
Tumor Intrinsic and Microenvironmental Mechanisms Driving Drug Combination Efficacy and Resistance in AML Oregon Health and Science University Tyner, Jeffrey Wallace; Druker, Brian J
An Integrated Translational Approach to Overcome Drug Resistance Massachusetts General Hospital Corcoran, Ryan Bruce; Flaherty, Keith T

The MSKCC-UW/Fred Hutch Prostate Cancer Drug Resistance and Sensitivity Center

Sloan-Kettering Institute for Cancer Research

Sawyers, Charles L

Bay Area Team Against Resistance

University of California - San Francisco Bivona, Trever G; Kuo, Calvin J
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