Evidence map›Paper›PMID 34071205›Full record

ArticleCancers2021

Therapeutic Targeting of Protein Disulfide Isomerase PDIA1 in Multiple Myeloma.

Metis Hasipek, Dale Grabowski, Yihong Guan, Raghunandan Reddy Alugubelli, Anand D Tiwari, Xiaorong Gu, Gabriel A DeAvila, Ariosto S Silva, Mark B Meads, Yvonne Parker and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
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

17 authors at 2 institutions in 1 country.

Metis HasipekDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.ORCID 0000-0003-3403-7381
Dale GrabowskiDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Yihong GuanDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.ORCID 0000-0001-8002-5141
Raghunandan Reddy AlugubelliDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Anand D TiwariDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Xiaorong GuDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Gabriel A DeAvilaDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Ariosto S SilvaDepartment of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Mark B MeadsDepartment of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Yvonne ParkerDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Daniel J LindnerDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.ORCID 0000-0002-8296-7703
Yogen SaunthararajahDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Kenneth H ShainDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Jaroslaw P MaciejewskiDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Frederic J ReuDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
James G PhillipsDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.
Babal K JhaDepartment of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH 44195, USA.ORCID 0000-0002-7660-5255
Cleveland Clinic · USMoffitt Cancer Center · US

Funding

cleveland clinic foundation start-up fundVelosano pilot award
6 · The paper itself

Abstract

Multiple myeloma is a genetically complex hematologic neoplasia in which malignant plasma cells constantly operate at the maximum limit of their unfolded protein response (UPR) due to a high secretory burden of immunoglobulins and cytokines. The endoplasmic reticulum (ER) resident protein disulfide isomerase, PDIA1 is indispensable for maintaining structural integrity of cysteine-rich antibodies and cytokines that require accurate intramolecular disulfide bond arrangement. PDIA1 expression analysis from RNA-seq of multiple myeloma patients demonstrated an inverse relationship with survival in relapsed or refractory disease, supporting its critical role in myeloma persistence. Using a structure-guided medicinal chemistry approach, we developed a potent, orally bioavailable small molecule PDIA1 inhibitor CCF642-34. The inhibition of PDIA1 overwhelms the UPR in myeloma cells, resulting in their apoptotic cell death at doses that do not affect the normal CD34

Indexed as

ERMMER stressIRMMprotein disulfide isomerase PDIA1UPR

Identifiers

PMID34071205
PMCPMC8198550
OpenAlexW3164464087

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.