ArticlePloS one2013
AKT signaling as a novel factor associated with in vitro resistance of human AML to gemtuzumab ozogamicin.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.Future oncology (London, England) · 2018Pooled it
- Feedback activation of MAPK-ERK1/2 signaling causes resistance to trastuzumab-deruxtecan in endometrial cancers.Gynecologic oncology · 2026Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- TROP2-targeting antibody-drug conjugates in breast cancer and ovarian carcinoma: therapeutic advances and resistance mechanisms.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Navigating the Landscape of Resistance Mechanisms in Antibody-Drug Conjugates for Cancer Treatment.Targeted oncology · 2025Review
- DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Antibody-drug conjugates in breast cancer: current resistance mechanisms and future combination strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Review
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response.The Journal of clinical investigation · 2023Review
- Update on the role of gemtuzumab-ozogamicin in the treatment of acute myeloid leukemia.Therapeutic advances in hematology · 2023Review
- Potential of antibody-drug conjugates (ADCs) for cancer therapy.Cancer cell international · 2022Review
- Article
- Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond.Vaccines · 2021Review
- Generation of Antibody-Drug Conjugate Resistant Models.Cancers · 2021Review
- CD33 Expression and Gentuzumab Ozogamicin in Acute Myeloid Leukemia: Two Sides of the Same Coin.Cancers · 2021Review
- Targeted Therapeutic Approach Based on Understanding of Aberrant Molecular Pathways Leading to Leukemic Proliferation in Patients with Acute Myeloid Leukemia.International journal of molecular sciences · 2021Review
- Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.Antibody therapeutics · 2021Article
- Acquired Resistance to Antibody-Drug Conjugates.Cancers · 2019Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Gemtuzumab ozogamicin (GO), an immunoconjugate between an anti-CD33 antibody and a calicheamicin-γ(1) derivative, induces remissions and improves survival in a subset of patients with acute myeloid leukemia (AML). As the mechanisms underlying GO and calicheamicin-γ(1) resistance are incompletely understood, we herein used flow cytometry-based single cell network profiling (SCNP) assays to study cellular responses of primary human AML cells to GO. Our data indicate that the extent of DNA damage is quantitatively impacted by CD33 expression and drug efflux activity. However, although DNA damage is required for GO-induced cytotoxicity, it is not sufficient for effective cell kill, suggesting that downstream anti-apoptotic pathways may function as relevant resistance mechanisms. Supporting this notion, we found activated PI3K/AKT signaling to be associated with GO resistance in vitro in primary AML cells. Consistently, the investigational AKT inhibitor MK-2206 significantly sensitized various human AML cells to GO or free calicheamicin-γ(1) with particularly pronounced effects in otherwise GO or free calicheamicin-γ(1)-resistant cells. Likewise, MK-2206 also sensitized primary AML cells to calicheamicin-γ(1). Together, our findings illustrate the capacity of SCNP assays to discover chemotherapy-related biological pathways and signaling networks relevant to GO-induced genotoxic stress. The identification of AKT signaling as being associated with GO resistance in vitro may provide a novel approach to improve the in vivo efficacy of GO/calicheamicin-γ(1) and, by extrapolation, other DNA damage-based therapeutics.
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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.