ReviewCancer science2017
Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.
Review in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed.
- Variable latency between the founder genetic event and rhabdoid tumor expansion.bioRxiv : the preprint server for biology · 2026Article
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- Treating microsatellite unstable metastatic parathyroid carcinoma with anti-PD1 therapy.JCEM case reports · 2026Article
- Review
- Multifocal micronodular pneumocyte hyperplasia in a patient with undiagnosed tuberous sclerosis: next-generation sequencing of a lung biopsy reveals TSC1 mutation-a case report.Journal of medical case reports · 2025Article
- Developing the trehalose biosynthesis pathway as an antifungal drug target.npj antimicrobials and resistance · 2025Review
- Current molecular understanding of central nervous system schwannomas.Acta neuropathologica communications · 2025Review
- The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.Genes & diseases · 2024Review
- Article
- Genetically transitional disease: conceptual understanding and applicability to rheumatic disease.Nature reviews. Rheumatology · 2024Review
- Comprehensive clinical phenotype, genotype and therapy in Yao syndrome.Frontiers in immunology · 2024Article
- Tsc2 mutation rather than Tsc1 mutation dominantly causes a social deficit in a mouse model of tuberous sclerosis complex.Human genomics · 2023Article
- The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer.Hereditary cancer in clinical practice · 2023Review
- Co-existence of 2 clinically significant variants causing disorders of somatic mosaicism.Genetics in medicine open · 2023Article
- Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro.Journal of neurological surgery. Part B, Skull base · 2022Article
- Resolving the biological paradox of aneurysm formation in children with tuberous sclerosis complex.JVS-vascular science · 2021Article
- Extreme value theory as a framework for understanding mutation frequency distribution in cancer genomes.PloS one · 2021Article
- Tumor-specific lytic path "hyperploid progression mediated death": Resolving side effects through targeting retinoblastoma or p53 mutant.World journal of clinical oncology · 2020Article
- Available Therapies for Patients with Neurofibromatosis-Related Nervous System Tumors.Current treatment options in oncology · 2020Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
On July 10, 2016, Alfred G. Knudson, Jr., MD, PhD, a leader in cancer research, died at the age of 93 years. We deeply mourn his loss. Knudson's two-hit hypothesis, published in 1971, has been fundamental for understanding tumor suppressor genes and familial tumor-predisposing syndromes. To understand the molecular mechanism of two-hit-initiated tumorigenesis, Knudson used an animal model of a dominantly inherited tumor, the Eker rat. From the molecular identification of Tsc2 germline mutations, the Eker rat became a model for tuberous sclerosis complex (TSC), a familial tumor-predisposing syndrome. Animal models, including the fly, have greatly contributed to TSC research. Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Although significant activity of these drugs has been reported, there are still problems such as recurrence of residual tumors and adverse effects. Recent studies indicate that there are mTORC1-independent signaling pathways downstream of hamartin/tuberin, which may represent new therapeutic targets. The establishment of cellular models, such as pluripotent stem cells with TSC2/Tsc2 gene mutations, will facilitate the understanding of new aspects of TSC pathogenesis and the development of novel treatment options. In this review, we look back at the history of Knudson and animal models of TSC and introduce recent progress in TSC research.
Indexed as
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.