ReviewFrontiers in oncology2013
The unpluggable in pursuit of the undruggable: tackling the dark matter of the cancer therapeutics universe.
Review in Frontiers in oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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
13 citing papers in PubMed.
- Disrupting the Undruggable: Emerging Modalities for Targeting Protein-Protein Interactions in Oncology.Biology · 2026Review
- Breast Cancer Predisposition Genes and Synthetic Lethality.International journal of molecular sciences · 2021Review
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm.Journal of immunotherapy and precision oncology · 2020Review
- Epigenetic synthetic lethality approaches in cancer therapy.Clinical epigenetics · 2019Review
- Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue-Going Beyond Apoptosis Induction.Frontiers in oncology · 2019Review
- Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration-Approved Drugs.Pharmacological reviews · 2017Review
- Exploiting Synthetic Lethality and Network Biology to Overcome EGFR Inhibitor Resistance in Lung Cancer.Journal of molecular biology · 2017Review
- Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter.Molecular carcinogenesis · 2016Article
- Targeting tumor suppressor genes for cancer therapy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- Cancer Cell Line Panels Empower Genomics-Based Discovery of Precision Cancer Medicine.Yonsei medical journal · 2015Review
- BCR-ABL inactivates cytosolic PTEN through Casein Kinase II mediated tail phosphorylation.Cell cycle (Georgetown, Tex.) · 2015Article
- The Repurposing Drugs in Oncology (ReDO) Project.Ecancermedicalscience · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The notion that targeted drugs can unplug gain-of-function tumor pathways has revitalized pharmaceutical research, but the survival benefits of this strategy have so far proven modest. A weakness of oncogene-blocking approaches is that they do not address the problem of cancer progression as selected by the recessive phenotypes of genetic instability and apoptotic resistance which in turn arise from loss-of-function - i.e., undruggable - defects of caretaker (e.g., BRCA, MLH1) or gatekeeper (e.g., TP53, PTEN) suppressor genes. Genetic instability ensures that rapid cell kill is balanced by rapid selection for apoptotic resistance and hence for metastasis, casting doubt on the assumption that cytotoxicity ("response") remains the best way to identify survival-enhancing drugs. In the absence of gene therapy, it is proposed here that caretaker-defective (high-instability) tumors may be best treated with low-lethality drugs inducing replicative (RAS-RAF-ERK) arrest or dormancy, causing "stable disease" rather than tumorilytic remission. Gatekeeper-defective (death-resistant) tumors, on the other hand, may be best managed by combining survival (PI3K-AKT-mTOR) pathway blockade with metronomic or sequential pro-apoptotic drugs.
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Identifiers
What OpenQuestion 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 OpenQuestion graph.