# The Cancer Target Discovery and Development Network at UCSF

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,026,728

## Abstract

PROJECT SUMMARY
Our general strategy is to take advantage of novel tools and methodologies that we have developed during our
first CTD^2 funding period- more specifically pioneering and applying CRISPR based technologies to aid the
discovery and characterization of novel cancer targets and their modulators– using innovative high throughput
screening methods. Our end goal is to uncover optimal combinations of perturbagens with the potential to
eliminate all cancer cells, despite their clonal heterogeneity and environmental context.
One goal is to elucidate new molecular targets with the goal to overcome acquired drug resistance. We build
upon an exciting system allowing us to quantitate genotypic and phenotypic cell heterogeneity for hundreds of
thousands of single cancer cells. We propose a battery of therapeutic small molecule screens to identify
candidate driver genes associated with drug resistance and with recurrent mutations from TCGA, TARGET,
CGCI, ICGC and related initiatives. The overall goal is to identify synthetic gene combinations necessary for
clinical resistance and related to inter- and intra-tumor heterogeneity.
We will develop and apply methodologies for the identification of genes influencing heterotypic cell-cell
interactions in tumors. Tumor evolution is a challenging area of research, largely due to the complexity of cell
types and behaviors. In this aim, high-throughput screens will be performed to identify non-cell autonomous
synthetic lethal and synthetic viable interactions relevant to tumor microenvironment interactions. These
studies will include primary T-effector/cancer cell interactions to identify new therapeutic targets and cancer
associated macrophage and fibroblast/cancer cell screens to identify genes mediating therapeutic resistance.
These systems are made possible by using a currently unpublished screening platform that may help to
identify genes important for cancer initiation, maintenance, and possibly metastasis. Since we will use primary
and cancer tissue, our unique platform will recapitulate as much as possible the characteristics of tumors in
patients and address an important challenge in cancer research.
We have developed a novel means to establish genetic epistatic interactions in mammalian cells and will
expand upon our efforts to generate specific libraries to map the subset of targets identified in the above
screens. In this aim, we will address targets and mechanisms by delineating where targets act in the pathway
by probing cancer-defining molecular interdependencies, using the novel targets and screening systems
described above. The end goal is to uncover the optimal combination of perturbagens with the potential to
eliminate all cancer cells, despite their clonal heterogeneity.

## Key facts

- **NIH application ID:** 10210200
- **Project number:** 5U01CA217882-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Sourav Bandyopadhyay
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,026,728
- **Award type:** 5
- **Project period:** 2017-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210200

## Citation

> US National Institutes of Health, RePORTER application 10210200, The Cancer Target Discovery and Development Network at UCSF (5U01CA217882-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10210200. Licensed CC0.

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