DNA replication stress and mitotic catastrophe mediate sotorasib addiction in KRASG12C-mutant cancer

Background Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRAS.sup.G12C-mutan...

Full description

Saved in:
Bibliographic Details
Published inJournal of biomedical science Vol. 30; no. 1; pp. 1 - 18
Main Authors Chiou, Li-Wen, Chan, Chien-Hui, Jhuang, Yu-Ling, Yang, Ching-Yao, Jeng, Yung-Ming
Format Journal Article
LanguageEnglish
Published Basel BioMed Central Ltd 29.06.2023
BioMed Central
BMC
Subjects
Addictions
Analysis
Annexin V
Apoptosis
Bioassays
Cancer
Cancer therapies
Care and treatment
Caspase
Cell culture
Cell cycle
Cell growth
Cell viability
Clinical trials
Comet assay
Cyclin-dependent kinase inhibitor p21
Damage
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA replication
Drug addiction
Drug approval
Drug resistance
Drug withdrawal
Flow cytometry
Genetic aspects
Growth factors
Health aspects
Hyperactivity
Immunofluorescence
Iodides
Kinases
KRAS
Lung cancer
Lung cancer, Non-small cell
MAP kinase
Mitosis
Mitotic catastrophe
Mutants
Non-small cell lung carcinoma
Pancreatic cancer
Propidium iodide
Protein kinases
Proteins
Replication
Replication stress
Sarcoma
Scientific equipment and supplies industry
Small cell lung carcinoma
Sotorasib
Substance abuse
Tumor cell lines
Withdrawal
Xenotransplantation
United States
United States > US
Taiwan
Online AccessGet full text

Cover

Abstract Background Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRAS.sup.G12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction. Methods Sotorasib-resistant cells were established using KRAS.sup.G12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo. Results In the absence of sotorasib, the sotorasib-resistant cells underwent p21.sup.Waf1/.sup.Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo. Conclusions We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer. Keywords: Sotorasib, Drug addiction, KRAS, Replication stress, Mitotic catastrophe
AbstractList Background Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRAS.sup.G12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction. Methods Sotorasib-resistant cells were established using KRAS.sup.G12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo. Results In the absence of sotorasib, the sotorasib-resistant cells underwent p21.sup.Waf1/.sup.Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo. Conclusions We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer. Keywords: Sotorasib, Drug addiction, KRAS, Replication stress, Mitotic catastrophe
Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.BACKGROUNDSotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.Sotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo.METHODSSotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo.In the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo.RESULTSIn the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo.We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.CONCLUSIONSWe elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRAS.sup.G12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction. Sotorasib-resistant cells were established using KRAS.sup.G12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo. In the absence of sotorasib, the sotorasib-resistant cells underwent p21.sup.Waf1/.sup.Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo. We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
Abstract Background Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction. Methods Sotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo. Results In the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo. Conclusions We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
BackgroundSotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.MethodsSotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo.ResultsIn the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo.ConclusionsWe elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
ArticleNumber 50
Audience Academic
Author Jhuang, Yu-Ling
Chan, Chien-Hui
Chiou, Li-Wen
Jeng, Yung-Ming
Yang, Ching-Yao
Author_xml – sequence: 1
  givenname: Li-Wen
  surname: Chiou
  fullname: Chiou, Li-Wen
– sequence: 2
  givenname: Chien-Hui
  surname: Chan
  fullname: Chan, Chien-Hui
– sequence: 3
  givenname: Yu-Ling
  surname: Jhuang
  fullname: Jhuang, Yu-Ling
– sequence: 4
  givenname: Ching-Yao
  surname: Yang
  fullname: Yang, Ching-Yao
– sequence: 5
  givenname: Yung-Ming
  orcidid: 0000-0002-9986-7194
  surname: Jeng
  fullname: Jeng, Yung-Ming
BookMark eNp9kl1rFDEUhgepYFv9A14NeOPN1HxOkitZVq3FouDHdchkTrZZZpI1yQr-ezO7FbpFJBdJTt7nDefwXjRnIQZompcYXWEs-zcZE0VUhwjtEFIMdexJc47ZcsVEnD04P2suct4ihLmS4rwZ331etQl2k7em-BjaXBLk3JowtrMvsXjb1hdTy3F3B-0MozcF2hxLTCb7oTXj6O0B9aH99HX17RqTdTfviwmlosFCet48dWbK8OJ-v2x-fHj_ff2xu_1yfbNe3XaWCVw6x6wFSin0BBNClcCEU-ekw9bYQQngho4jBQkDJ4r1Ag8KOCNDjznDDOhlc3P0HaPZ6l3ys0m_dTReHwoxbbRJtaMJNJXKgBkQYo6zvucSCObSAOKEOmCoer09eu32Q23aQijJTCempy_B3-lN_KUxokiKXlSH1_cOKf7cQy569tnCNJkAcZ81kZRwoSjtq_TVI-k27lOos1pUUlQlfqDamNqBDy7Wj-1iqleCc4qlEKyqrv6hqmuE2dsaG-dr_QSQR8CmmHMCp60vhzBU0E-1Ib1kTB8zpmvG9CFjekHJI_TvfP4D_QH04NRY
CitedBy_id crossref_primary_10_1038_s41388_024_03041_0
crossref_primary_10_3390_cancers15164141
crossref_primary_10_1158_2767_9764_CRC_24_0411
crossref_primary_10_1007_s11060_024_04672_9
crossref_primary_10_32604_biocell_2024_048758
Cites_doi 10.1038/s41586-021-04065-2
10.2741/3814
10.1158/0008-5472.CAN-06-2351
10.1016/j.cbpa.2021.02.010
10.1038/nature11814
10.1038/327293a0
10.3390/cancers13143504
10.2174/1381612825666190506122228
10.1158/1078-0432.CCR-21-3074
10.1097/CAD.0000000000000951
10.1073/pnas.1003428107
10.1038/s41698-022-00328-x
10.1038/nrd4389
10.1038/sj.onc.1203723
10.1038/s41586-019-1884-x
10.1016/j.cell.2015.05.053
10.1038/nature05327
10.1038/s41416-022-02032-w
10.1038/s41417-021-00383-9
10.7554/eLife.33718
10.1038/s41467-019-09438-w
10.1158/0008-5472.CAN-11-2612
10.1016/j.devcel.2020.01.004
10.1016/j.celrep.2013.03.004
10.1016/j.ebiom.2019.09.023
10.1074/jbc.274.53.38083
10.1158/1541-7786.MCR-18-0327
10.1038/nature08833
10.1126/science.2406906
10.1016/0092-8674(88)90571-5
10.1002/jcp.20622
10.1158/1541-7786.MCR-07-2036
10.1038/ncomms13087
10.1158/2159-8290.CD-17-0682
10.1016/j.dnarep.2014.04.008
10.1038/nature12796
10.1590/1678-4685-gmb-2019-0138
10.1681/ASN.V561288
10.1016/j.ccell.2014.11.018
10.1158/1078-0432.CCR-20-2077
10.1088/2057-1739/2/3/035004
10.1056/NEJMoa2103695
10.1038/nm.4369
ContentType Journal Article
Copyright COPYRIGHT 2023 BioMed Central Ltd.
2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2023. The Author(s).
The Author(s) 2023
Copyright_xml – notice: COPYRIGHT 2023 BioMed Central Ltd.
– notice: 2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2023. The Author(s).
– notice: The Author(s) 2023
DBID AAYXX
CITATION
3V.
7QL
7QO
7QP
7T5
7TK
7TM
7U7
7U9
7X7
7XB
88E
8FD
8FE
8FG
8FH
8FI
8FJ
8FK
8G5
ABJCF
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BGLVJ
BHPHI
C1K
CCPQU
DWQXO
FR3
FYUFA
GHDGH
GNUQQ
GUQSH
H94
HCIFZ
K9.
L6V
LK8
M0S
M1P
M2O
M7N
M7P
M7S
MBDVC
P64
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PTHSS
Q9U
RC3
7X8
5PM
DOA
DOI 10.1186/s12929-023-00940-4
DatabaseName CrossRef
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Biotechnology Research Abstracts
Calcium & Calcified Tissue Abstracts
Immunology Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Toxicology Abstracts
Virology and AIDS Abstracts
Health & Medical Collection (ProQuest)
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
Technology Research Database
ProQuest SciTech Collection
ProQuest Technology Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Research Library
Materials Science & Engineering Collection
ProQuest Central (Alumni)
ProQuest One Sustainability
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central Database Suite (ProQuest)
Technology Collection
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Central
Engineering Research Database
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
ProQuest Research Library
AIDS and Cancer Research Abstracts
SciTech Collection (ProQuest)
ProQuest Health & Medical Complete (Alumni)
ProQuest Engineering Collection
ProQuest Biological Science Collection
ProQuest Health & Medical Collection
Medical Database
Research Library
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biological Science Database
Engineering Database
Research Library (Corporate)
Biotechnology and BioEngineering Abstracts
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
Engineering Collection
ProQuest Central Basic
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
Publicly Available Content Database
Research Library Prep
ProQuest Central Student
ProQuest Central Essentials
Nucleic Acids Abstracts
SciTech Premium Collection
Environmental Sciences and Pollution Management
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
Health Research Premium Collection
Natural Science Collection
Health & Medical Research Collection
Biological Science Collection
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Engineering Collection
Engineering Database
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
ProQuest Technology Collection
Health Research Premium Collection (Alumni)
Biological Science Database
Neurosciences Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
Engineering Research Database
ProQuest One Academic
Calcium & Calcified Tissue Abstracts
ProQuest One Academic (New)
Technology Collection
Technology Research Database
ProQuest One Academic Middle East (New)
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
Research Library (Alumni Edition)
ProQuest Natural Science Collection
ProQuest Central
ProQuest Health & Medical Research Collection
Genetics Abstracts
ProQuest Engineering Collection
Biotechnology Research Abstracts
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
ProQuest Research Library
ProQuest Central Basic
Toxicology Abstracts
ProQuest SciTech Collection
ProQuest Medical Library
Materials Science & Engineering Collection
Immunology Abstracts
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic


Publicly Available Content Database
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: 8FG
  name: ProQuest Technology Collection
  url: https://search.proquest.com/technologycollection1
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
Biology
EISSN 1423-0127
EndPage 18
ExternalDocumentID oai_doaj_org_article_389aeab004f546658e2158ae0523fe40
PMC10308767
A755318774
10_1186_s12929_023_00940_4
GeographicLocations United States
United States--US
Taiwan
GeographicLocations_xml – name: United States
– name: Taiwan
– name: United States--US
GroupedDBID ---
.86
0R~
29J
29K
2NJ
2WC
36B
4.4
5GY
5VS
7X7
88E
8FE
8FG
8FH
8FI
8FJ
8G5
AAFWJ
AAYXX
ABDBF
ABJCF
ABJNI
ABOCM
ABUWG
ACGFO
ACGFS
ACIHN
ACIWK
ACPRK
ACUHS
ADBBV
ADIMF
ADRAZ
ADUKV
AEAQA
AEGNC
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHBYD
AHMBA
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AMKLP
AMTXH
AOIJS
AZQEC
B0M
BAPOH
BAWUL
BBNVY
BCNDV
BENPR
BFQNJ
BGLVJ
BGNMA
BHPHI
BMC
BPHCQ
BVXVI
C6C
CCPQU
CITATION
CS3
CYUIP
D-I
DIK
DU5
DWQXO
E3Z
EAD
EAP
EBC
EBD
EBLON
EBS
EMB
EMK
EMOBN
EPL
ESX
F5P
FYUFA
GNUQQ
GROUPED_DOAJ
GUQSH
GX1
HCIFZ
HMCUK
HYE
IAO
IEA
IHE
IHR
INH
INR
ITC
IZQ
KDC
KQ8
L6V
LAK
LK8
M1P
M2O
M48
M4Y
M7P
M7S
ML~
NU0
O5R
O5S
OK1
P19
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PTHSS
RBZ
RHV
RNS
ROL
RPM
RPX
RRX
RSV
S27
SBL
SDH
SOJ
SV3
T13
TR2
TUS
UKHRP
VC2
WJK
WK8
~8M
~KM
PMFND
3V.
7QL
7QO
7QP
7T5
7TK
7TM
7U7
7U9
7XB
8FD
8FK
C1K
FR3
H94
K9.
M7N
MBDVC
P64
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQUKI
Q9U
RC3
7X8
PUEGO
5PM
ID FETCH-LOGICAL-c471t-f4cce333e621223971253ff8f1cacb97e5a3dd3e8eb5294671b9e542b615414e3
IEDL.DBID M48
ISSN 1423-0127
1021-7770
IngestDate Wed Aug 27 01:06:51 EDT 2025
Thu Aug 21 18:37:45 EDT 2025
Sun Aug 24 03:50:36 EDT 2025
Fri Jul 25 19:01:42 EDT 2025
Tue Jun 17 20:43:51 EDT 2025
Tue Jun 10 20:38:23 EDT 2025
Thu Apr 24 22:59:46 EDT 2025
Tue Jul 01 00:21:25 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1
Language English
License Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c471t-f4cce333e621223971253ff8f1cacb97e5a3dd3e8eb5294671b9e542b615414e3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0000-0002-9986-7194
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1186/s12929-023-00940-4
PQID 2838783216
PQPubID 54111
PageCount 18
ParticipantIDs doaj_primary_oai_doaj_org_article_389aeab004f546658e2158ae0523fe40
pubmedcentral_primary_oai_pubmedcentral_nih_gov_10308767
proquest_miscellaneous_2832579336
proquest_journals_2838783216
gale_infotracmisc_A755318774
gale_infotracacademiconefile_A755318774
crossref_citationtrail_10_1186_s12929_023_00940_4
crossref_primary_10_1186_s12929_023_00940_4
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2023-06-29
PublicationDateYYYYMMDD 2023-06-29
PublicationDate_xml – month: 06
  year: 2023
  text: 2023-06-29
  day: 29
PublicationDecade 2020
PublicationPlace Basel
PublicationPlace_xml – name: Basel
– name: London
PublicationTitle Journal of biomedical science
PublicationYear 2023
Publisher BioMed Central Ltd
BioMed Central
BMC
Publisher_xml – name: BioMed Central Ltd
– name: BioMed Central
– name: BMC
References AK Ashley (940_CR26) 2014; 21
GP Leung (940_CR29) 2019; 17
MJ Sale (940_CR32) 2019; 10
JY Xue (940_CR14) 2020; 577
DA Erlanson (940_CR8) 2021; 62
F Dietlein (940_CR27) 2015; 162
AD Cox (940_CR7) 2014; 13
F Weinberg (940_CR33) 2010; 107
F Skoulidis (940_CR10) 2021; 384
P Kotsantis (940_CR37) 2016; 7
HK Matthews (940_CR21) 2020; 52
G Moriceau (940_CR18) 2015; 27
LMF Primo (940_CR34) 2019; 43
JM Ostrem (940_CR9) 2013; 503
Y Zhao (940_CR12) 2021; 599
IA Prior (940_CR3) 2012; 72
S Chen (940_CR6) 2019; 25
JL Bos (940_CR2) 1987; 327
I Smalley (940_CR42) 2019; 48
Y Adachi (940_CR16) 2020; 26
DA Farnsworth (940_CR31) 2022; 6
EC Nakajima (940_CR11) 2022; 28
M Das Thakur (940_CR20) 2013; 494
C Schäfer (940_CR22) 2016; 2
A Abulaiti (940_CR38) 2006; 66
HI Saavedra (940_CR39) 1999; 274
Y Xue (940_CR43) 2017; 23
J Liu (940_CR13) 2022; 29
JH Overmeyer (940_CR23) 2008; 6
CH Chan (940_CR15) 2023; 128
MV Milburn (940_CR5) 1990; 247
AM Unni (940_CR30) 2018; 7
R Di Micco (940_CR35) 2006; 444
A Hong (940_CR17) 2018; 8
Y Zou (940_CR25) 2006; 208
G Hatzivassiliou (940_CR28) 2010; 464
HI Saavedra (940_CR40) 2000; 19
B Margolis (940_CR4) 1994; 5
JH Overmeyer (940_CR24) 2011; 16
KM Aird (940_CR36) 2013; 3
C Almoguera (940_CR1) 1988; 53
M Rao (940_CR19) 2020; 31
SK Garattini (940_CR41) 2021; 13
References_xml – volume: 599
  start-page: 679
  issue: 7886
  year: 2021
  ident: 940_CR12
  publication-title: Nature
  doi: 10.1038/s41586-021-04065-2
– volume: 16
  start-page: 1693
  issue: 5
  year: 2011
  ident: 940_CR24
  publication-title: Front Biosci (Landmark Ed)
  doi: 10.2741/3814
– volume: 66
  start-page: 10505
  issue: 21
  year: 2006
  ident: 940_CR38
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-06-2351
– volume: 62
  start-page: 101
  year: 2021
  ident: 940_CR8
  publication-title: Curr Opin Chem Biol
  doi: 10.1016/j.cbpa.2021.02.010
– volume: 494
  start-page: 251
  issue: 7436
  year: 2013
  ident: 940_CR20
  publication-title: Nature
  doi: 10.1038/nature11814
– volume: 327
  start-page: 293
  issue: 6120
  year: 1987
  ident: 940_CR2
  publication-title: Nature
  doi: 10.1038/327293a0
– volume: 13
  start-page: 3504
  issue: 14
  year: 2021
  ident: 940_CR41
  publication-title: Cancers (Basel)
  doi: 10.3390/cancers13143504
– volume: 25
  start-page: 1105
  issue: 10
  year: 2019
  ident: 940_CR6
  publication-title: Curr Pharm Des
  doi: 10.2174/1381612825666190506122228
– volume: 28
  start-page: 1482
  issue: 8
  year: 2022
  ident: 940_CR11
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-21-3074
– volume: 31
  start-page: 1026
  issue: 10
  year: 2020
  ident: 940_CR19
  publication-title: Anticancer Drugs
  doi: 10.1097/CAD.0000000000000951
– volume: 107
  start-page: 8788
  issue: 19
  year: 2010
  ident: 940_CR33
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1003428107
– volume: 6
  start-page: 88
  issue: 1
  year: 2022
  ident: 940_CR31
  publication-title: NPJ Precis Oncol
  doi: 10.1038/s41698-022-00328-x
– volume: 13
  start-page: 828
  issue: 11
  year: 2014
  ident: 940_CR7
  publication-title: Nat Rev Drug Discov
  doi: 10.1038/nrd4389
– volume: 19
  start-page: 3948
  issue: 34
  year: 2000
  ident: 940_CR40
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1203723
– volume: 577
  start-page: 421
  issue: 7790
  year: 2020
  ident: 940_CR14
  publication-title: Nature
  doi: 10.1038/s41586-019-1884-x
– volume: 162
  start-page: 146
  issue: 1
  year: 2015
  ident: 940_CR27
  publication-title: Cell
  doi: 10.1016/j.cell.2015.05.053
– volume: 444
  start-page: 638
  issue: 7119
  year: 2006
  ident: 940_CR35
  publication-title: Nature
  doi: 10.1038/nature05327
– volume: 128
  start-page: 148
  issue: 1
  year: 2023
  ident: 940_CR15
  publication-title: Br J Cancer
  doi: 10.1038/s41416-022-02032-w
– volume: 29
  start-page: 875
  issue: 7
  year: 2022
  ident: 940_CR13
  publication-title: Cancer Gene Ther
  doi: 10.1038/s41417-021-00383-9
– volume: 7
  year: 2018
  ident: 940_CR30
  publication-title: Elife
  doi: 10.7554/eLife.33718
– volume: 10
  start-page: 2030
  issue: 1
  year: 2019
  ident: 940_CR32
  publication-title: Nat Commun
  doi: 10.1038/s41467-019-09438-w
– volume: 72
  start-page: 2457
  issue: 10
  year: 2012
  ident: 940_CR3
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-11-2612
– volume: 52
  start-page: 563
  issue: 5
  year: 2020
  ident: 940_CR21
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2020.01.004
– volume: 3
  start-page: 1252
  issue: 4
  year: 2013
  ident: 940_CR36
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2013.03.004
– volume: 48
  start-page: 178
  year: 2019
  ident: 940_CR42
  publication-title: EBioMedicine
  doi: 10.1016/j.ebiom.2019.09.023
– volume: 274
  start-page: 38083
  issue: 53
  year: 1999
  ident: 940_CR39
  publication-title: J Biol Chem
  doi: 10.1074/jbc.274.53.38083
– volume: 17
  start-page: 199
  issue: 1
  year: 2019
  ident: 940_CR29
  publication-title: Mol Cancer Res
  doi: 10.1158/1541-7786.MCR-18-0327
– volume: 464
  start-page: 431
  issue: 7287
  year: 2010
  ident: 940_CR28
  publication-title: Nature
  doi: 10.1038/nature08833
– volume: 247
  start-page: 939
  issue: 4945
  year: 1990
  ident: 940_CR5
  publication-title: Science
  doi: 10.1126/science.2406906
– volume: 53
  start-page: 549
  issue: 4
  year: 1988
  ident: 940_CR1
  publication-title: Cell
  doi: 10.1016/0092-8674(88)90571-5
– volume: 208
  start-page: 267
  issue: 2
  year: 2006
  ident: 940_CR25
  publication-title: J Cell Physiol
  doi: 10.1002/jcp.20622
– volume: 6
  start-page: 965
  issue: 6
  year: 2008
  ident: 940_CR23
  publication-title: Mol Cancer Res
  doi: 10.1158/1541-7786.MCR-07-2036
– volume: 7
  start-page: 13087
  year: 2016
  ident: 940_CR37
  publication-title: Nat Commun
  doi: 10.1038/ncomms13087
– volume: 8
  start-page: 74
  issue: 1
  year: 2018
  ident: 940_CR17
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-17-0682
– volume: 21
  start-page: 131
  year: 2014
  ident: 940_CR26
  publication-title: DNA Repair (Amst)
  doi: 10.1016/j.dnarep.2014.04.008
– volume: 503
  start-page: 548
  issue: 7477
  year: 2013
  ident: 940_CR9
  publication-title: Nature
  doi: 10.1038/nature12796
– volume: 43
  issue: 1 suppl 1
  year: 2019
  ident: 940_CR34
  publication-title: Genet Mol Biol
  doi: 10.1590/1678-4685-gmb-2019-0138
– volume: 5
  start-page: 1288
  issue: 6
  year: 1994
  ident: 940_CR4
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.V561288
– volume: 27
  start-page: 240
  issue: 2
  year: 2015
  ident: 940_CR18
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2014.11.018
– volume: 26
  start-page: 5962
  issue: 22
  year: 2020
  ident: 940_CR16
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-20-2077
– volume: 2
  issue: 3
  year: 2016
  ident: 940_CR22
  publication-title: Converg Sci Phys Oncol
  doi: 10.1088/2057-1739/2/3/035004
– volume: 384
  start-page: 2371
  issue: 25
  year: 2021
  ident: 940_CR10
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa2103695
– volume: 23
  start-page: 929
  issue: 8
  year: 2017
  ident: 940_CR43
  publication-title: Nat Med
  doi: 10.1038/nm.4369
SSID ssj0015987
Score 2.391262
Snippet Background Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung...
Sotorasib is the first KRAS.sup.G12C inhibitor approved by the US Food and Drug Administration for treating KRAS.sup.G12C-mutant non-small-cell lung cancer...
BackgroundSotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer...
Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC)....
Abstract Background Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung...
SourceID doaj
pubmedcentral
proquest
gale
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Enrichment Source
Index Database
StartPage 1
SubjectTerms Addictions
Analysis
Annexin V
Apoptosis
Bioassays
Cancer
Cancer therapies
Care and treatment
Caspase
Cell culture
Cell cycle
Cell growth
Cell viability
Clinical trials
Comet assay
Cyclin-dependent kinase inhibitor p21
Damage
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA replication
Drug addiction
Drug approval
Drug resistance
Drug withdrawal
Flow cytometry
Genetic aspects
Growth factors
Health aspects
Hyperactivity
Immunofluorescence
Iodides
Kinases
KRAS
Lung cancer
Lung cancer, Non-small cell
MAP kinase
Mitosis
Mitotic catastrophe
Mutants
Non-small cell lung carcinoma
Pancreatic cancer
Propidium iodide
Protein kinases
Proteins
Replication
Replication stress
Sarcoma
Scientific equipment and supplies industry
Small cell lung carcinoma
Sotorasib
Substance abuse
Tumor cell lines
Withdrawal
Xenotransplantation
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3NaxUxEA9SqHiRWhVXq0QQPEjobj52s8fX1lqU9qAWegvZZIIFu0_ex6H_fWey-x5dBb143UyW3cxMfjPJfDD2zpc6JWhK0SGaCG1jJaw2nWhlUHUjO5Vyb8Dzi_rsUn--Mlf3Wn1RTNhQHnhYuEMEVA-ehCsZXSNeAoKU9UDHmQl09tYR8zbO1Hh_YNCV3qTI2PpwiagmW4H4JCiUrhR6AkO5Wv-fe_LvcZL3gOd0jz0eLUY-G770CXsA_T7bHXpI3u6zh-fj7fhTFk8uZnwB2xtpPiSCcN9HfoOaiy_gdFyDj6maAM9ZIyvgyzk63h51g1N0UU504Nc9__J19u1TJY_FzZpaDeNUFJDFM3Z5-vH78ZkYuyiIgMCzEkmHAEopqBGlJJofaNKolGyqgg9d24DxKkYFFjojW9w3q64Fo2WHto6uNKjnbKef9_CCcVmCiTra6BHZq6a0XtmovEltIL8kFKzaLKoLY4lx6nTx02VXw9ZuYIRDRrjMCKcL9mE759dQYOOv1EfEqy0lFcfOD1Bk3Cgy7l8iU7D3xGlHKoyfh8swZCLgT1IxLDdrDO5MFg3jgh1MKFH1wnR4IytuVP2lQ3vNNtT_qS7Y2-0wzaRwth7m60yDW2WrFNLYiYxN_mw60l__yOW_q1zFsW5e_o-1eMUeyawWtZDtAdtZLdbwGs2sVfcma9QdW0ghdA
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Health & Medical Collection (ProQuest)
  dbid: 7X7
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lb9QwELagCMQFQQGxpSAjIXFAVhPbSZwTWgqlArUHoNLeLMcel0o0afdx4N8z42QDAanXeJzXPL6xPQ_GXrtMxwhVJhpEE6FNyIXRRSNq6VVZyUbF1Bvw5LQ8PtOfF8Vi2HBbDWGVW5uYDHXoPO2RHyAMmora6pTvrq4FdY2i09WhhcZtdodKl1FIV7UYF1yI1KlBHnWvRi-yyrZJM6Y8WCHOyVogYgkKrsuEngBTqt__v5X-N3LyLyg6esgeDD4kn_dMf8RuQbvL7vZdJX_tsnsnw3n5YxY-nM75EsYzat6nhnDXBn6Juow34LSBg5epvgBPeSRr4KsOl-IOtYVTvFFKfeAXLf_ydf7tUy4PxeWGmg_jVBSZ5RN2dvTx--GxGPoqCI9QtBZRew9KKSgRtyQ6JOjkqBhNzL3zTV1B4VQICgw0hazRkuZNDYWWDXo_OtegnrKdtmvhGeMygyLoYIJDrM-rzDhlgnJFrD2tVPyM5dufav1QdJx6X_y0afFhStszwiIjbGKE1TP2dpxz1ZfcuJH6PfFqpKRy2elCtzy3g_ZZ9MocOLJQsdAlOl2Ano5xQHviEXQ2Y2-I05aUGl8Pf0Ofm4AfSeWx7Lwq0FYZdJVnbH9Cicrop8NbWbGDMVjZP6I7Y6_GYZpJAW4tdJtEg8azVgppzETGJl82HWkvfqSC4Hmq61hWezc__Tm7L5PAl0LW-2xnvdzAC3Sp1s3LpDe_AfMGG4o
  priority: 102
  providerName: ProQuest
Title DNA replication stress and mitotic catastrophe mediate sotorasib addiction in KRASG12C-mutant cancer
URI https://www.proquest.com/docview/2838783216
https://www.proquest.com/docview/2832579336
https://pubmed.ncbi.nlm.nih.gov/PMC10308767
https://doaj.org/article/389aeab004f546658e2158ae0523fe40
Volume 30
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3db9MwED_tQyBeEAzQCqMyEhIPyJDYTuI8INSNtROoFRpU6pvlJA5M2lJIW4n999w5SSEwIV7yEJ-txPf188fdATy3gSpLlwQ8Q2_ClS5CrlWU8VTkMk5EJktfG3A6i8_m6v0iWuxAV-6oncDVjUs7qic1ry9f_fh-_RYV_o1XeB2_XqHPEilH78PpolzA1S7so2dKSFGn6tepQpT6gnmhIspQJF0QzY1j9ByVz-f_t9X-8yblb65pfA_utpiSjRohuA87rjqAW02VyesDuD1tz88fQPFuNmK1255ZsyZUhNmqYFeo2zgAow0dfE35BpiPK1k7tlri0tyi9jC6f-RDIdhFxT6cjz5NQnHCrzZUjBi7ogjVD2E-Pv18csbbOgs8R9e05qXKcyeldDH6MYEABUGPLEtdhrnNszRxkZVFIZ12WSRStKxhlrpIiQzRkAqVk49gr1pW7hCYCFxUqEIXNiAGBNpKXUgblWlOK5d8AGE3qSZvk5BTLYxL4xcjOjYNIwwywnhGGDWAl9s-35oUHP-kPiZebSkpfbZ_say_mFYbDaI06yxZrDJSMYIwh8hHW0d75KVTwQBeEKcNiR1-Hk5DE6uAP0npsswoidB2aYTOAzjqUaJy5v3mTlZMJ9sGEZ1OqEJUPIBn22bqSRfeKrfceBo0pqmUSKN7Mtb7s35LdfHVJwgPfZ7HOHn8H8M_gTvCS33MRXoEe-t6454izlpnQ9hNFgk-9XgyhP3j09nH86Hfs8DnZBEOvXL9BPgwJf4
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELZKEY8LggIiUMBIIA7IamI7iXNAaGkpW7a7B2ilvbmO40AlmpR9CPVP8RuZcR4QkHrrNbazG8_jGz9mPkJemlCWpUtDlgOaMKmKiCkZ5yzjViQpz0XpuQGns2R8LD_N4_kG-dXlwuC1ys4nekdd1Bb3yHcABlWKtDrJu_MfDFmj8HS1o9Bo1GLiLn7Ckm359mAP5PuK8_0PR7tj1rIKMAuOeMVKaa0TQrgEvDYHOAaIF2Wpysgam2epi40oCuGUy2OOBPRRnrlY8hywX0bSCXjvNXIdgDdEi0rn_QIPIgNPyIds2RC1pmGXpKOSnSXgKs8YICTDy3whkwMg9HwB_6PCvzc1_4K-_bvkThuz0lGjZPfIhqu2yI2GxfJii9yctufz90mxNxvRhevPxGmTikJNVdAz8B3wAoobRvAY6xlQn7eycnRZw9LfgHVSvN_kUy3oaUUnn0dfPkZ8l52tkewYhoKKLh6Q4yuZ8Ydks6or94hQHrq4kIUqDMQWURoqI1QhTFxmFldGNiBRN6natkXOkWvju_aLHZXoRhAaBKG9ILQMyJt-zHlT4uPS3u9RVn1PLM_tH9SLr7q1dg1RoHEGPWIZywSCPAeRlTIO9-BLJ8OAvEZJa3Qi8PdgGppcCPhILMelR2kMvlFBaB6Q7UFPMH47bO50RbfOZ6n_mEpAXvTNOBIv1FWuXvs-4KwzIaCPGujY4MuGLdXpN1-APPJ1JJP08eW__pzcGh9ND_XhwWzyhNzmXvkTxrNtsrlarN1TCOdW-TNvQ5ScXLXR_gZ0KFfP
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DNA+replication+stress+and+mitotic+catastrophe+mediate+sotorasib+addiction+in+KRASG12C-mutant+cancer&rft.jtitle=Journal+of+biomedical+science&rft.au=Chiou%2C+Li-Wen&rft.au=Chan%2C+Chien-Hui&rft.au=Jhuang%2C+Yu-Ling&rft.au=Yang%2C+Ching-Yao&rft.date=2023-06-29&rft.issn=1423-0127&rft.eissn=1423-0127&rft.volume=30&rft.issue=1&rft.spage=50&rft_id=info:doi/10.1186%2Fs12929-023-00940-4&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1423-0127&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1423-0127&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1423-0127&client=summon