ReviewGenes2021
Drugging the Undruggable: Advances on RAS Targeting in Cancer.
Review in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 77 citations in OpenAlex.
- The anticancer effects of PCAIs in pancreatic cancer cells involve MAPK and PI3K/AKT pathways hyperactivation.Oncotarget · 2026Article
- A Molecular-Protein Fusion Framework for Rapid Virtual Screening: Accelerating Lead Discovery for "Undruggable'' Oncogenic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting the NF-κB pathway represents a potential strategy to attenuate HGF-induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026Review
- KRAS G12C Inhibition in Solid Tumors: Biological Breakthroughs, Clinical Evidence, and Open Challenges.Cancers · 2025Review
- Investigation of potential KRASG12D inhibitors: a comparative study between MRTX1133 and natural compounds via computational structural biology approaches.BMC research notes · 2025Article
- Drugging the 'undruggable' KRAS: breakthroughs, challenges, and opportunities in pancreatic cancer.Cancer biology & medicine · 2025Review
- Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Advances in the treatment of KRASCancer · 2025Review
- Recent Advances in Peptide Inhibitors Targeting Wild-Type Ras Protein Interactions in Cancer Therapy.International journal of molecular sciences · 2025Review
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies.Recent patents on anti-cancer drug discovery · 2025Review
- Lung cancer organoid-based drug evaluation models and new drug development application trends.Translational lung cancer research · 2024Review
- Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer.Scientific reports · 2024Article
- Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses.Science advances · 2024Article
- SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers.Nature communications · 2024Article
- Endogenous oncogenic KRAS expression increases cell proliferation and motility in near-diploid hTERT RPE-1 cells.The Journal of biological chemistry · 2024Article
- Facts and Hopes in Immunotherapy Strategies Targeting Antigens Derived from KRAS Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Combinatorial strategies to target RAS-driven cancers.Nature reviews. Cancer · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Around 20% of all malignancies harbour activating mutations in RAS isoforms. Despite this, there is a deficiency of RAS-targeting agents licensed for therapeutic use. The picomolar affinity of RAS for GTP, and the lack of suitable pockets for high-affinity small-molecule binding, precluded effective therapies despite decades of research. Recently, characterisation of the biochemical properties of KRAS-G12C along with discovery of its 'switch-II pocket' have allowed development of effective mutant-specific inhibitors. Currently seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval. Here, we discuss historical efforts to target RAS directly and approaches to target RAS effector signalling, including combinations that overcome limitations of single-agent targeting. We also review pre-clinical and clinical evidence for the efficacy of KRAS-G12C inhibitor monotherapy followed by an illustration of combination therapies designed to overcome primary resistance and extend durability of response. Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms.
Indexed as
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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.