Evidence map›Paper›PMID 32462369›Full record

ArticleInvestigational new drugs2020

Chemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells.

Seung-Woo Hong, Jae-Sik Shin, Jai-Hee Moon, Soo-A Jung, Dong-In Koh, Yeaseong Ryu, Yoon Sun Park, Do Yeon Kim, Sang-Soo Park, Jun Ki Hong and 12 more

Abstract read
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In one paragraph

Article in Investigational new drugs, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

22 authors at 4 institutions in 1 country.

Seung-Woo Hong *Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Jae-Sik Shin *Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Jai-Hee Moon *Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Soo-A JungInstitute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Dong-In KohAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Yeaseong RyuAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Yoon Sun ParkAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Do Yeon KimAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Sang-Soo ParkAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Jun Ki HongAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Eun Ho KimAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Mi Jin KimAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Hong-Rae JeongAsan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
In Hwan BaeHanmi Research Center, Hanmi Pharm. Co., Ltd, Gyeonggi-do, Republic of Korea.
Young-Gil AhnHanmi Research Center, Hanmi Pharm. Co., Ltd, Gyeonggi-do, Republic of Korea.
Kwee Hyun SuhHanmi Research Center, Hanmi Pharm. Co., Ltd, Gyeonggi-do, Republic of Korea.
Ig-Jun ChoOsong Medical Innovation Foundation, Cheongju-si, Republic of Korea.
Jong-Soon KangBioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, Republic of Korea.
Yong Sang HongInstitute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Jung Shin LeeInstitute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea.
Dong-Hoon JinInstitute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea. inno183@amc.seoul.kr.ORCID http://orcid.org/0000-0002-1124-1518
Tae Won KimInstitute for Innovative Cancer Research, Asan Medical Center, Seoul, Republic of Korea. twkimmd@amc.seoul.kr.
Asan Medical Center · KRHanmi Pharmaceutical (South Korea) · KRKorea Research Institute of Bioscience and Biotechnology · KROsong Medical Innovation Foundation · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inhibitor of apoptosis proteins (IAPs) are overexpressed in the majority of cancers and prevent apoptosis by inhibiting caspases. IAPs have therefore attracted considerable attention as potential targets for anticancer therapy. Here, we demonstrated that HM90822 (abbreviated HM822; a new synthetic IAP antagonist) induced apoptotic cell death via proteasome-dependent degradation of BIR2/3 domain-containing IAPs in human pancreatic cancer cells. HM822 inhibited the expression of XIAP and cIAP1/2 proteins in Panc-1 and BxPC-3 cells, which are sensitive to HM822. HM822 also induced IAP ubiquitination and promoted proteasome-dependent IAP degradation. However, cells expressing phospho-XIAP (Ser87) and AKT exhibited resistance to HM822. In other words, the overexpression of AKT-CA (constitutive active form for AKT) or AKT-WT induced resistance to HM822. In addition, in Panc-1 xenograft and orthotopic mouse models, we revealed that tumor growth was suppressed by the administration of HM822. Taken together, these results suggest that HM822 induces apoptosis through ubiquitin/proteasome-dependent degradation of BIR3 domain-containing IAPs. These findings suggest that phospho-XIAP and phospho-AKT may be used as biomarkers for predicting the efficacy of HM822 in pancreatic cancer patients.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorDrug Resistance, NeoplasmFemaleHumansInhibitor of Apoptosis ProteinsMice, Inbred BALB CMice, NudePancreatic NeoplasmsPhosphorylationProto-Oncogene Proteins c-aktTumor BurdenUbiquitinationAntineoplastic AgentsInhibitor of Apoptosis ProteinsProto-Oncogene Proteins c-aktapoptosisHM90822 (HM822)IAPspancreatic cancerubiquitination

Identifiers

PMID32462369
OpenAlexW3030779785

What OpenQuestion holds

Textmetadata
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.