Evidence map›Paper›PMID 37190191›Full record

ArticleCancers2023

Novel CDK12/13 Inhibitors AU-15506 and AU-16770 Are Potent Anti-Cancer Agents in EGFR Mutant Lung Adenocarcinoma with and without Osimertinib Resistance.

Tapan K Maity, Eun Young Kim, Constance M Cultraro, Abhilash Venugopalan, Leena Khare, Ramulu Poddutoori, Sivapriya Marappan, Samiulla D Syed, William G Telford, Susanta Samajdar and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Tapan K MaityThoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Eun Young KimThoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.ORCID 0000-0002-3281-5744
Constance M CultraroThoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Abhilash VenugopalanThoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Leena KhareAurigene Discovery Technologies Ltd., Bangalore 560100, India.
Ramulu PoddutooriAurigene Discovery Technologies Ltd., Bangalore 560100, India.
Sivapriya MarappanAurigene Discovery Technologies Ltd., Bangalore 560100, India.
Samiulla D SyedAurigene Discovery Technologies Ltd., Bangalore 560100, India.
William G TelfordExperimental Transplantation & Immunotherapy Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Susanta SamajdarAurigene Discovery Technologies Ltd., Bangalore 560100, India.
Murali RamachandraAurigene Discovery Technologies Ltd., Bangalore 560100, India.
Udayan GuhaThoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Aurigene Discovery Technologies (India) · INCenter for Cancer Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osimertinib is a third-generation epidermal growth factor receptor and tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of lung adenocarcinoma patients harboring EGFR mutations. However, acquired resistance to this targeted therapy is inevitable, leading to disease relapse within a few years. Therefore, understanding the molecular mechanisms of osimertinib resistance and identifying novel targets to overcome such resistance are unmet needs of cancer patients. Here, we investigated the efficacy of two novel CDK12/13 inhibitors, AU-15506 and AU-16770, in osimertinib-resistant EGFR mutant lung adenocarcinoma cells in culture and xenograft models in vivo. We demonstrate that these drugs, either alone or in combination with osimertinib, are potent inhibitors of osimertinib-resistant as well as -sensitive lung adenocarcinoma cells in culture. Interestingly, only the CDK12/13 inhibitor in combination with osimertinib, although not as monotherapy, suppresses the growth of resistant tumors in xenograft models in vivo. Taken together, the results of this study suggest that inhibition of CDK12/13 in combination with osimertinib has the potential to overcome osimertinib resistance in EGFR mutant lung adenocarcinoma patients.

Indexed as

AU15506AU16770CDK12CDK13EGFRinhibitorlung cancerosimertinibresistance

Identifiers

PMID37190191
PMCPMC10137182
OpenAlexW4365454431

What OpenQuestion holds

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Registered trials

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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.