The purpose of this Notice of Special Interest (NOSI) is to: (1) encourage investigators to apply single-cell proteomics for interrogation of premalignant and early malignant lesions; (2) develop new multiparametric biomarkers for cancer screening, early detection and risk assessment; and, (3) establish a biomarkers workflow for a wide coverage of disease variability and individuals at the population level.

Background

Recent advances in single-cell genomic and transcriptomic technologies enabled a better understanding of the cellular content of tumorigenic lesions, including early detection of clonal evolution, detection of the emergence of drug-resistant cells and improved phenotypic characterization of the lesion’s cellular heterogeneity. Single-cell mass spectroscopy-based proteomics and antibody-based targeted proteomics are emerging as powerful complementary approaches for the characterization of individual cell types within a lesion, their intercellular networks, and their dynamic physiological state. In addition, these approaches can be used to identify, map and visualize aberrant subcellular structures, intracellular networks, molecular interactomes, and proteoforms some with cancer-associated posttranslational modifications that cannot be predicted by genomic/transcriptomic analysis. The detected molecular, structural and functional aberrations are potential cancer markers and targets for prevention and therapy.

Research topics that are relevant to this NOSI include, but are not limited to:

• Discovery of biomarkers that could be used to predict progression among patients on active surveillance;
• Molecular and cellular signatures for early emergence of clonal diversity among cells in human precursor, benign and early cancerous lesions;
• Identification of targets for immunoprevention based on the analysis of human precursor, benign and early cancerous lesions;
• Development of an integrated approach (including but not limited to imaging and path omics) for multiparametric biomarker discovery based on spatial and temporal changes in human precursor, benign and early cancerous lesions;
• Development and application of Deep Learning approaches for improved classification of precursor and benign cancerous lesions as well as the development of new cancer biomarkers for screening, early detection and risk assessment.

Application and Submission Information

This notice applies to due dates on or after May 25, 2020 and subsequent receipt dates through May 8, 2023.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this Notice:

FOA	Title	First Available Due Date	Expiration Date
PA-19-052	NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)	June 16, 2020	January 8, 2022
PA-19-053	NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)	June 16, 2020	January 8, 2022
PA-19-054	NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)	June 16, 2020	January 8, 2022
PA-19-056	NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)	June 5, 2020	January 8, 2022
PAR-19-113	Cancer Tissue Engineering Collaborative: Enabling Biomimetic Tissue-Engineered Technologies for Cancer Research (R01 Clinical Trials Optional) *	June 5, 2020	January 8, 2022
PAR-19-251	Basic and Translational Research on Adducts in Cancer Risk Identification and Prevention (R01 Clinical Trial Optional) *	July 2, 2020	November 9, 2021
PAR-19-252	Basic and Translational Research on Adducts in Cancer Risk Identification and Prevention R21 Clinical Trails Optional) *	July 2, 2020	November 9, 2021
PAR-19-264	Imaging, Biomarkers and Digital Pathomics for the Early Detection of Premetastatic Aggressive Cancer (R01 Clinical Trials Optional) *	July 10, 2020	December 11, 2021
RFA-CA-20-005	Research Answers to National Cancer Institute's (NCI) Provocative Questions (R21 Clinical Trial Optional) *	November 17, 2020	November 18, 2020
PAR-20-052	NCI Small Grants Program for Cancer Research for Years 2020, 2021, and 2022 (NCI Omnibus R03 Clinical Trial Optional)	June 24, 2020	January 8, 2023
PAR-20-053	Program to Assess the Rigor and Reproducibility of Extracellular Vesicle-Derived Analytes for Cancer Detection (R01 Clinical Trial Not Allowed) *	June 5, 2020	January 8, 2023
PAR-20-077	National Cancer Institute Program Project Applications (P01 Clinical Trial Optional)	May 25, 2020	May 8, 2023

* Note: Investigators planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with NCI Program Directors of the parent award before writing and submitting their applications to allow for the determination of appropriateness and interest of the NCI in any related proposed research.

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-CA-20-044” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Although NCI is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.