Targeting DNA Damage Repair Mechanisms in Pancreas Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
Aim and Scope
2. Materials and Methods
Composition of the Expert Panel and Recommendations
3. Results
3.1. The Incidence of Germline BRCA1/2 Mutations
3.2. BRCA1/2 Testing Recommendations
3.3. Genetic Counselling for Patients with a Germline BRCA1/2 Mutation
3.4. Analysing Homologous Recombination Repair Pathways
3.5. Treatment of PDAC Patients with BRCA1/2 Mutations
3.6. Treatment of PDAC Patients with Other Mutations in DDR Genes
3.7. Acquired Resistance to PARP Inhibitor Therapy
3.8. Future Directions
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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# | Question |
---|---|
Q1 | Do you know the proportion of gBRCA1/2 mutation in PDAC in your area/country? |
Q2 | Do you regularly determine the BRCA mutation status in patients with PDAC? |
Q2-1 | If no, explain why not. |
Q3 | In which situation do you search for BRCA mutation? |
Q4 | Is your approach different to patients with a suspicion of genetic syndrome and those without any suspicion? |
Q4-1 | If yes, what is the difference? |
Q5 | Which material do you use for BRCA analysis? |
Q6 | Who performs the test? |
Q7 | What is your acceptable/desirable period of waiting for the results? |
Q8 | In your opinion, does family history play a role in identifying patients with PDAC and gBRCA1/2 mutation? |
Q9 | Are patients with gBRCA1/2 mutation regularly referred to a human geneticist in your country? |
Q10 | For your testing, do you send the patient to the geneticist before or after checking the results positively? |
Q11 | Do the panels you use comprise other DDR-related genes? |
Q12 | Do you determine genomic signatures for HRDness in a given PDAC? |
Q12-1 | If yes, what is the reason? |
Q13 | Do you pay attention to differences in the BRCA mutational status? |
Q13-1 | If yes, explain why. Do you think it influences prognosis? |
Q14 | In the case of a known BRCA mutation, is there a preference for a specific chemotherapy combination? |
Q15 | Is prolongation of PFS compared to placebo a clinically meaningful endpoint for you? |
Q16 | Do you treat patients with germline BRCA1/2 mutations with PARP inhibitors as a maintenance treatment? |
Q17 | Should patients with somatic BRCA1/2 mutations be treated as patients with gBRCA1/2 mutations? |
Q18 | Do somatic (or germline) mutations in other DDR genes have a therapeutic consequence (e.g., ATM)? |
Q18-1 | If yes, what is the proposed treatment? |
Q19 | Do mutations in DDR genes sensitise genes to checkpoint inhibitors? |
Q20 | Which developments do you foresee in the area of DNA damage repair deficiency in PDAC without gBRCA mutation? |
Q21 | Do you think we need to consider this BRCA status in a (neo)adjuvant setting for a possible application/trial? |
“APC” “ATM” “BAP1” “BARD1” “BLM” “BMPR1A” “BRCA1” “BRCA2” “BRIP1” “CBL” “CDC73” “CDH1” “CDK4” “CDKN1B” “CDKN2A” “CHEK2” “CTNNA1” “DICER1” “EPCAM” “ERCC2” “ERCC3” “ERCC4” “ERCC5” “FAM175A” “FANCA” “FANCC” “FANCD2” “FANCE” “FANCF” “FANCG” “FANCI” “FANCL” “FH” “FLCN” “FLT3” “GREM1” “HOXB13” “IDH1” “IDH2” “LZTR1” “MAP2K1” “MAPK1” “MAX” “MEN1” “MITF” “MLH1” “MRE11” “MSH2” “MSH6” “MUTYH” “NBN” “NF1” “NF2” “PALB2” “PMS2” “POLD1” “POLE” “PRKAR1A” “PTCH1” “PTEN” “RAD50” “RAD51C” “RAD51D” “RAF1” “RB1” “RECQL4” “RNF43” “RUNX1” “SDHA” “SDHAF2” “SDHB” “SDHC” “SDHD” “SLX4” “SMAD3” “SMAD4” “SMARCA4” “SMARCB1” “STK11” “SUFU” “TERT” “TGFBR1” “TGFBR2” “TMEM127” “TP53” “TSC1” “TSC2” “VHL” “WT1” “XRCC2” |
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Perkhofer, L.; Golan, T.; Cuyle, P.-J.; Matysiak-Budnik, T.; Van Laethem, J.-L.; Macarulla, T.; Cauchin, E.; Kleger, A.; Beutel, A.K.; Gout, J.; et al. Targeting DNA Damage Repair Mechanisms in Pancreas Cancer. Cancers 2021, 13, 4259. https://doi.org/10.3390/cancers13174259
Perkhofer L, Golan T, Cuyle P-J, Matysiak-Budnik T, Van Laethem J-L, Macarulla T, Cauchin E, Kleger A, Beutel AK, Gout J, et al. Targeting DNA Damage Repair Mechanisms in Pancreas Cancer. Cancers. 2021; 13(17):4259. https://doi.org/10.3390/cancers13174259
Chicago/Turabian StylePerkhofer, Lukas, Talia Golan, Pieter-Jan Cuyle, Tamara Matysiak-Budnik, Jean-Luc Van Laethem, Teresa Macarulla, Estelle Cauchin, Alexander Kleger, Alica K. Beutel, Johann Gout, and et al. 2021. "Targeting DNA Damage Repair Mechanisms in Pancreas Cancer" Cancers 13, no. 17: 4259. https://doi.org/10.3390/cancers13174259