ArticleCancer discovery2024
Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 44 citations in OpenAlex.
- Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs.International journal of cancer · 2026Article
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- WEE1 kinase inhibition to overcome acquired resistance to targeted therapies in colorectal cancer.EMBO molecular medicine · 2026Article
- Deciphering programmed cell death for gastric cancer prognosis: AKR1B1 as a key player.Journal of applied genetics · 2026Article
- POU2F1 Promotes Chemoresistance in Colorectal Cancer Cells via Attenuates the MDR2 Degradation Mediated by PPP1R11 Lactylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inducible CRISPR-Cas9 screening platform to interrogate non-proliferative cellular states.Nature protocols · 2026Review
- Uev1A counteracts oncogeniceLife · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dying cells as architects of the stem cell niche: a conserved mechanism driving tissue regeneration and tumor therapy resistance.Cell communication and signaling : CCS · 2026Review
- Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R-Loop Accumulation and DNA Repair Deficiencies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- A pan-cancer atlas of metabolic regulatory circuitries integrating multi-omic, immune, and clinical dimensions.Frontiers in molecular biosciences · 2026Article
- High-throughput transcriptomic screening reveals entrectinib as a repositioning opportunity in 19q12 autism spectrum disorder.Scientific reports · 2025Article
- Dehydroascorbic Acid Induces Cell Death in Sarcoma Stem Cells Under bFGF-Mediated Stemness-Supporting Conditions.Antioxidants (Basel, Switzerland) · 2025Article
- CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.Nature biotechnology · 2025Article
- Article
Corrections and comments
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Authors and funding
38 authors at 10 institutions in 6 countries.
Funding
Abstract
Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.