J. M. McFarland

Click chemistry selectively activates an auristatin protodrug with either intratumoral or systemic tumor-targeting agents

This paper demonstrates the activation of a protodrug, SQP22, using click chemistry with tumor-targeting agents, showing anti-tumor effects in murine models with reduced toxicity.

Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal

This study compares CRISPR-Cas9 and RNAi screens to identify cancer vulnerabilities, finding that RNAi better detects pan-dependencies while CRISPR identifies more dependencies overall.

Phosphate dysregulation via the XPR1:KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer

The paper identifies XPR1 and KIDINS220 as therapeutic targets in ovarian cancer by showing their role in phosphate dysregulation leading to cell death.

The tumor microenvironment drives transcriptional phenotypes and their plasticity in metastatic pancreatic cancer

This study identifies a transitional cancer cell state in metastatic pancreatic cancer and shows that tumor microenvironment signals drive transcriptional plasticity and subtype transitions.

Selective vulnerability of aneuploid human cancer cells to inhibition of the spindle assembly checkpoint

This study identifies aneuploid cancer cells as more vulnerable to spindle assembly checkpoint (SAC) inhibition and explores the underlying mechanisms.

Global computational alignment of tumor and cell line transcriptional profiles

The paper develops an unsupervised alignment method to compare tumor and cell line transcriptional profiles, revealing differences in similarity across cancer types and identifying cell lines with distinct transcriptional states.

Multiplexed single-cell profiling of post-perturbation transcriptional responses to define cancer vulnerabilities and therapeutic mechanism of action

The paper introduces MIX-Seq, a method for multiplexed single-cell transcriptional profiling of cancer cell responses to perturbations, revealing drug mechanisms and predicting cell viability.

Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity

The paper uses single-cell RNA-seq to analyze cancer cell lines and identifies recurring expression programs of heterogeneity that mirror those in tumors, suggesting intrinsic plasticity contributes to intra-tumoral diversity.

Non-oncology drugs are a source of previously unappreciated anti-cancer activity

The paper identifies non-oncology drugs with anti-cancer activity across 578 cancer cell lines using PRISM, finding that many drugs selectively inhibit cancer cells based on molecular features.

Patient-derived xenografts undergo murine-specific tumor evolution

This study shows that PDX tumors acquire new genomic changes over passages, differ from human tumors, and affect drug responses.