A New NCI Research Resource

Responses to Oncology Agents and Dosing in Models to Aid Preclinical Studies (ROADMAPS)

More than 30 years of drug response and toxicity data in human xenograft models are now available to the scientific community.

A Gap in the Literature: Data from Mouse Models for Drug Development

Preclinical xenograft studies in mouse models are vital to the development of new chemotherapeutic agents. Results of these experiments are often the first indicators of in vivo antitumor efficacy and of drug-induced toxicities. However, these data are not always reported in the scientific literature or, when reported, often focus on response data without detailed experimental conditions that would be of value to other researchers conducting preclinical studies.

Decades of Data

The NCI’s Biological Testing Branch (BTB), led by Dr. Melinda Hollingshead, has compiled response and toxicity data from more than 30 years of BTB preclinical studies evaluating anti-cancer agents. These efforts include testing investigational agents, many of which have received FDA approval, and identifying novel applications for existing drugs.

This expansive data set, which includes more than 3,000 unique combinations of tumor models, drugs, and dosing regimens in mice, comprises:

• 70 FDA-approved agents, many developed with DTP support
  • cytotoxic agents (e.g., methotrexate, doxorubicin, cyclophosphamide, cisplatin)
  • targeted agents (e.g., imatinib, everolimus, pazopanib, dasatinib)
  • drugs used in the adjuvant setting (e.g., tamoxifen, abiraterone)
• 140 tumor models
  • of which 52 are in the NCI-60 Human Tumor Cell Lines Screen
  • 121 human cell lines and 19 patient-derived xenografts (PDX)
  • multiple models from 12 distinct tumor histologies

A Unique Research Resource

NCI recently made these data available in an online searchable database as a resource for the extramural research community. The database — Responses to Oncology Agents and Dosing in Models to Aid Preclinical Studies (ROADMAPS) — offers a consolidated resource for dosing information and response data. This information is intended to facilitate the design and conduct of future preclinical studies using these agents. Details on the history and utility of the ROADMAPS database are described in Cancer Research (Hollingshead, et al; 2022).

BTB tested each model reported in ROADMAPS against different agents following differing administration regimens, routes, doses, and vehicles. The searchable data include:

• Agent name
• Dosing regimen
• Route of administration
• Tumor model and histology
• Tumor response
• Drug-induced mortality
• Body weight changes
• Vehicle formulation

The extensive data shared in ROADMAPS can help investigators select tolerable and active dosing regimens for single- and combination-drug studies and sensitive tumor types. Toxic dose levels and responsiveness data can be used to guide preclinical studies.

ROADMAPS Data Will Expand

The initial ROADMAPS database released to the public in May 2022 contains data through December 2021. Since targeted agents tend to be newer and tested against fewer models than older agents, BTB is evaluating the efficacy of targeted agents against an array of tumor models. As BTB expands its repertoire of drug studies in PDX models, additional ROADMAPS data will be made publicly available in periodic updates.

Contact: Melinda Hollingshead, DVM, PhD, Branch Chief, BTB (hollingm@mail.nih.gov)