ArticleACS central science2016
Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.
Article in ACS central science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 33 citations in OpenAlex.
- Design, synthesis, and antiproliferative activity of new 5-ethylsulfonyl-indazole-3-carbohydrazides as dual EGFR/VEGFR-2 kinases inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- PAC-1 Synergizes with Sunitinib to Enhance Cell Death in Pancreatic Neuroendocrine Tumors.ACS pharmacology & translational science · 2025Article
- Resistance to FOXM1 inhibitors in breast cancer is accompanied by impeding ferroptosis and apoptotic cell death.Breast cancer research and treatment · 2024Article
- Raptinal: a powerful tool for rapid induction of apoptotic cell death.Cell death discovery · 2024Review
- Mathematical modeling predicts pathways to successful implementation of combination TRAIL-producing oncolytic virus and PAC-1 to treat granulosa cell tumors of the ovary.Cancer biology & therapy · 2023Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.British journal of cancer · 2023Article
- Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients.Neuro-oncology · 2021Article
- Procaspase-Activating Compound-1 Synergizes with TRAIL to Induce Apoptosis in Established Granulosa Cell Tumor Cell Line (KGN) and Explanted Patient Granulosa Cell Tumor Cells In Vitro.International journal of molecular sciences · 2021Article
- Companion canines: an under-utilised model to aid in translating anti-metastatics to the clinic.Clinical & experimental metastasis · 2020Article
- Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.Frontiers in oncology · 2020Review
- Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential.ACS chemical biology · 2019Review
- Metastasis in the wild: investigating metastasis in non-laboratory animals.Clinical & experimental metastasis · 2019Review
- Immunohistochemical Characterization of Procaspase-3 Overexpression as a Druggable Target With PAC-1, a Procaspase-3 Activator, in Canine and Human Brain Cancers.Frontiers in oncology · 2019Article
- Article
- TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.International journal of molecular medicine · 2018Article
- Overcoming Resistance to Targeted Anticancer Therapies through Small-Molecule-Mediated MEK Degradation.Cell chemical biology · 2018Article
- Article
- Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model.Current opinion in hematology · 2017Review
- Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.Neuro-oncology advancesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Conventional chemotherapeutics remain essential treatments for most cancers, but their combination with other anticancer drugs (including targeted therapeutics) is often complicated by unpredictable synergies and multiplicative toxicities. As cytotoxic anticancer chemotherapeutics generally function through induction of apoptosis, we hypothesized that a molecularly targeted small molecule capable of facilitating a central and defining step in the apoptotic cascade, the activation of procaspase-3 to caspase-3, would broadly and predictably enhance activity of cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1) enhances cancer cell death induced by 15 different FDA-approved chemotherapeutics, across many cancer types and chemotherapeutic targets. In particular, the promising combination of PAC-1 and doxorubicin induces a synergistic reduction in tumor burden and enhances survival in murine tumor models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of 4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC-1 with doxorubicin resulted in no additional toxicity. On the basis of the mode of action of PAC-1 and the high expression of procaspase-3 in many cancers, these results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a potent and general strategy to enhance therapeutic response.
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.