PMID- 37231946
OWN - NLM
STAT- MEDLINE
DCOM- 20230810
LR  - 20230810
IS  - 2296-5262 (Electronic)
IS  - 2296-5270 (Linking)
VI  - 46
IP  - 7-8
DP  - 2023
TI  - Combining Poly-(ARD-Ribose) Polymerase and Programmed Cell Death Protein 1 
      Inhibition in a Patient with Esophagogastric Adenocarcinoma.
PG  - 320-325
LID - 10.1159/000530801 [doi]
AB  - INTRODUCTION: Esophagogastric adenocarcinoma (EGA) is one of the leading causes 
      of cancer-related mortality worldwide. Therapeutic options are limited for 
      patients with recurrent or metastatic disease. Targeted therapy may be a suitable 
      treatment for selected patients, but its efficacy remains elusive. CASE 
      PRESENTATION: Here, a 52-year-old male patient with advanced EGA Siewert Type II 
      shows a significant response to combination therapy with olaparib and 
      pembrolizumab. After progression following first- and second-line therapy, 
      including a programmed cell death ligand 1 (PD-L1) inhibitor, next-generation 
      sequencing of a tumor sample was performed to identify possible molecular 
      targets. A mutation in RAD51C, a member of the homology-directed repair (HDR) 
      system, was identified in addition to high PD-L1 expression. As a result, therapy 
      with the poly-(ARD-Ribose) polymerase (PARP) inhibitor olaparib and the 
      programmed cell death protein 1 (PD1)-inhibitor pembrolizumab was initiated. A 
      durable partial response lasting for more than 17 months was observed. A second 
      molecular profiling from a newly occurring subcutaneous metastasis showed a loss 
      of FGF10 but no fluctuations in the gene alteration of RAD51C and SMARCA4. 
      Interestingly, the new lesion showed HER2-positivity (immunohistochemistry 3+ and 
      fluorescence in situ hybridization [FISH]-positivity) in 30% of tumor cells. 
      CONCLUSION: In this case, a long-lasting response to the combination of olaparib 
      and pembrolizumab was observed despite previous treatment with a PD-L1 inhibitor. 
      This case illustrates the need for further clinical trials to analyze the 
      efficacy of PARP inhibitor combinations in EGA.
CI  - (c) 2023 S. Karger AG, Basel.
FAU - Artzenroth, Jule Cecilia
AU  - Artzenroth JC
AD  - University Cancer Center Hamburg (UCCH), University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Tintelnot, Joseph
AU  - Tintelnot J
AD  - University Cancer Center Hamburg (UCCH), University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Haag, Georg Martin
AU  - Haag GM
AD  - Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Gokkurt, Eray
AU  - Gokkurt E
AD  - University Cancer Center Hamburg (UCCH), University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
AD  - Hamatologisch-Onkologische Praxis Eppendorf, Hamburg, Germany.
FAU - Steffens, Johann
AU  - Steffens J
AD  - Radiologische Praxis am Israelitisches Krankenhaus, Hamburg, Germany.
FAU - Stein, Alexander
AU  - Stein A
AD  - University Cancer Center Hamburg (UCCH), University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
AD  - Hamatologisch-Onkologische Praxis Eppendorf, Hamburg, Germany.
LA  - eng
PT  - Case Reports
DEP - 20230509
PL  - Switzerland
TA  - Oncol Res Treat
JT  - Oncology research and treatment
JID - 101627692
RN  - 681HV46001 (Ribose)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - EC 3.6.1.- (SMARCA4 protein, human)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Ribose
MH  - B7-H1 Antigen/metabolism
MH  - Programmed Cell Death 1 Receptor
MH  - In Situ Hybridization, Fluorescence
MH  - *Adenocarcinoma/pathology
MH  - DNA Helicases
MH  - Nuclear Proteins/genetics
MH  - Transcription Factors/genetics
OTO - NOTNLM
OT  - Esophagogastric adenocarcinoma
OT  - Poly-(ARD-Ribose) polymerase inhibitors
OT  - Programmed cell death protein 1/L1 inhibitors
EDAT- 2023/05/26 06:42
MHDA- 2023/08/10 06:43
CRDT- 2023/05/26 03:51
PHST- 2023/01/11 00:00 [received]
PHST- 2023/04/12 00:00 [accepted]
PHST- 2023/08/10 06:43 [medline]
PHST- 2023/05/26 06:42 [pubmed]
PHST- 2023/05/26 03:51 [entrez]
AID - 000530801 [pii]
AID - 10.1159/000530801 [doi]
PST - ppublish
SO  - Oncol Res Treat. 2023;46(7-8):320-325. doi: 10.1159/000530801. Epub 2023 May 9.