CTD²: Cancer Target Discovery and Development

The Cancer Target Discovery and Development (CTD²) Network, a functional genomics initiative, bridges the gap between cancer genomics and biology. The Network aims to understand how tumor heterogeneity leads to drug resistance in order to develop optimal combinations of chemotherapy or small molecules in combination with immunotherapy.

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News & Publications

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Dai et al. (2021) Cell Rep. CC BY-NC-ND 4.0

CTD²

July 27, 2021

SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization

Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 is correlated with changes in altered histopathological transitions, metastatic disease, and poor prognosis. In this study, we use isogenic cancer cell...

Mohanty et al. (2021) Cell Reports Medicine. CC BY-NC-ND 4.0

CTD²

July 20, 2021

Uncoupling of gene expression from copy number presents therapeutic opportunities in aneuploid cancers

Uncoupling of mRNA expression from copy number (UECN) might be a strategy for cancer cells to a tolerate high degree of aneuploidy. To test the extent and role of UECN across cancers, we perform integrative multiomic analysis of The Cancer Genome Atlas (TCGA) dataset, encompassing ∼5,000...

CTD²

June 01, 2021

A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation*

Mutations in ARID1A rank among the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated ARID1A knockout (KO) in primary TP53^-/- human...

Graphical Abstract for "Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages"

CTD²

May 27, 2021

Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages

Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor...

CTD²

May 20, 2021

Hypomorph mutation-directed small-molecule protein-protein interaction inducers to restore mutant SMAD4-suppressed TGF-β signaling

Tumor suppressor genes represent a major class of oncogenic drivers. However, direct targeting of loss-of-function tumor suppressors remains challenging. To address this gap, we explored a variant-directed chemical biology approach to reverse the lost function of tumor suppressors using SMAD4 as...