Notice Number: NOT-CA-14-032
Release Date: February 18, 2014
Response Date: April 18, 2014
National Cancer Institute (NCI)
The goal of this Request for Information (RFI) is to gain feedback, comments, and novel ideas from members of cancer research communities with regard to possible directions and expansion of programs for screening of novel anticancer agents that are supported by the National Cancer Institute (NCI) through the Developmental Therapeutics Program (DTP) of the Division of Cancer Treatment and Diagnosis (DCTD). Specifically, opinions are sought on the possibility of expanded access to the DTP screening capabilities at the Frederick National Laboratory for Cancer Research (FNLCR) and on-site, in-person programs for interested extramural investigators.
The information gained through this RFI is expected to be used by the DTP to develop programs and to expand drug screening opportunities that will serve the needs of broad cancer research communities by assisting investigators working on the discovery and development of new anticancer agents.
This RFI is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government, the National Institutes of Health (NIH), and/or the National Cancer Institute (NCI).
DTP has provided drug-screening services to the cancer community for several decades and has assisted investigators in other aspects related to anti-cancer drug discovery and development. The "NCI-60" screen, utilizing a panel of 60 human tumor cell lines, has been the primary vehicle for assessing the ability of small molecules, biologics, and natural product extracts to kill or inhibit the growth of human cancer cell lines. Initially envisioned as a disease-oriented screen, the extensive molecular characterization of the panel has allowed the transition to a more target-oriented understanding of drug responses.
Recently, DTP has undertaken extensive testing of drug combinations in the NCI-60 panel. For this combination testing program, DTP has acquired over 500 investigational drugs now in clinical development as well as all Food and Drug Administration (FDA)-approved anticancer agents (>100) in quantities appropriate for both in vitro and in vivo screening to be conducted at the FNLCR. These agents may be used to interrogate a wide range of mechanistic categories. Based on NIH policy, these agents cannot be distributed to the extramural community directly, but can be used at FNLCR in support of projects by extramural investigators.
The NCI is considering reprogramming a portion of the DCTD drug screening resources to conduct specific drug screening-related projects proposed by extramural investigators. The current plans anticipate that approximately 50 projects (similar in scope to the scenarios 1-5 listed below) might be conducted per year.
Examples of scenarios for anticipated projects include, but are not limited to:
1. Drug combination screening (targeted approach). An investigator might provide an isogenic pair of cell lines differing in the status of a particular cancer-associated gene. Several agents targeting pathways upstream or downstream of the affected gene would be selected. These agents would each be tested in the isogenic cell lines in combination with FDA-approved drugs and/or investigational drugs to identify drug pairs that could be candidates for additional preclinical testing and a possible path for the combination to the clinic, in trials stratified according to mutation status.
2. Drug combination screening (broad approach using the NCI-60 panel). An investigator could provide a novel drug to the screening program and request that it be combined with the DTP set of approved and investigational drugs for screening against the NCI-60 panel.
3. Screening to overcome clinically-relevant mechanisms of drug resistance. A researcher could provide NCI with a small set of cell lines that represent the spectrum of clinically-relevant resistance mechanisms seen in patients to a particular targeted drug. NCI would screen cell lines harboring such changes with the targeted drug (to which the cell lines are now resistant) in combination with approved and investigational drugs to identify combinations that might be candidates for treating drug-resistant patients.
4. Responses of distinct cellular models to the DTP set of approved and investigational drugs. An investigator could provide NCI with a small set of cell lines and request screening for responses to the DTP set of approved and investigational drugs. Cell lines might be derived from genetically engineered mouse models (e.g., to represent heterogeneity within the disease), from circulating human tumor cells, from patient-derived xenografts, or from rare tumor types
5. Molecular responses to targeted therapies. Researchers could request cell extracts prepared from cells treated with a drug of interest in order to study the molecular responses to a targeted therapy. A small number of drug-sensitive and resistant lines would be chosen, either from the NCI-60 panel, or from another source. Cells would be treated with several concentrations of the agent and samples collected at several time points following drug treatment. Samples would be processed to provide multiple sets from each cell line that would be suitable for a variety of analytic endpoints (e.g. mRNA, protein, miRNA) to be assayed in the investigators’ laboratories. Sufficient samples would be collected to enable multiple laboratories to utilize the materials, according to their expertise.
This RFI targets investigators developing and/or conducting studies with new anticancer agents, researchers developing biological models for such studies, and other interested members of cancer research community. The responses are entirely voluntary and may be anonymous. If you are willing to do so, you may indicate the environment to which your perspective pertains to (academia, clinical research, etc.).
Respondents are encouraged to provide their perspective on the aspects listed below. However, anyone willing to respond has a full discretion to address any aspects deemed relevant to the theme of the RFI, even if such aspects are not expressly mentioned below.
Responses will be accepted through April 18, 2014. Please mark responses with the RFI identifier NOT-CA-14-032. Responses in electronic formats are preferred and can be emailed to firstname.lastname@example.org.
You will receive electronic confirmation acknowledging receipt of your response but will not be notified of the results of this RFI. All information will be processed and analyzed to ensure anonymity and confidentiality. No proprietary, classified, confidential, and/or sensitive information should be included in your response.
All individual responses will remain confidential. Any identifiers (e.g., names, institutions, e-mail addresses, etc.) will be removed when responses are compiled. Only the processed, anonymized results will be shared internally with NIH staff members and members of scientific working groups convened by the NCI, as appropriate.
Please direct all inquiries to:
National Cancer Institute (NCI)
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