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PDAC QSP Model — Annotated References

Pancreatic Ductal Adenocarcinoma (PDAC) Quantitative Systems Pharmacology Model
Compiled for the QSP Disease Model Library · Last updated: 2026-06-23
Total references: 40

1. Epidemiology & Clinical Overview

  • [Siegel 2023] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 73(1):17–48. PMID: 36633525 PubMed

  • [Rahib 2014] Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921. PMID: 24840647 PubMed

  • [Ryan 2014] Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 371(11):1039–1049. PMID: 25084709 PubMed

  • [Mizrahi 2020] Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet 395(10242):2008–2020. PMID: 32593337 PubMed

  • [Strobel 2019] Strobel O, Neoptolemos J, Jager D, Buchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol 16(1):11–26. PMID: 30341417 PubMed

2. PDAC Biology & Driver Mutations

  • [Almoguera 1988] Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53(4):549–554. PMID: 3162073 PubMed

  • [Biankin 2012] Biankin AV, Waddell N, Kassahn KS, et al.; Australian Pancreatic Cancer Genome Initiative. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 491(7424):399–405. PMID: 23103869 PubMed

  • [Waddell 2015] Waddell N, Pajic M, Patch AM, et al.; Australian Pancreatic Cancer Genome Initiative. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518(7540):495–501. PMID: 25079552 PubMed

  • [Bailey 2016] Bailey P, Chang DK, Nones K, et al.; Australian Pancreatic Cancer Genome Initiative. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531(7592):47–52. PMID: 26909576 PubMed

  • [Moffitt 2015] Moffitt RA, Marayati R, Flate EL, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet 47(10):1168–1178. PMID: 26343385 PubMed

  • [Witkiewicz 2015] Witkiewicz AK, McMillan EA, Balaji U, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun 6:6744. PMID: 25855536 PubMed

3. Tumor Stroma & Desmoplasia

  • [Bhatt 2011] Bhatt RS, Wang X, Zhang L, et al. Renal cancer resistance to antiangiogenic therapy is delayed by restoration of angiostatic signaling. Mol Cancer Ther 9(10):2793–2802. PMID: 21372152 PubMed

  • [Neesse 2011] Neesse A, Michl P, Frese KK, et al. Stromal biology and therapy in pancreatic cancer. Gut 60(6):861–868. PMID: 20946153 PubMed

  • [Provenzano 2012] Provenzano PP, Cuevas C, Chang AE, Bhatt VK, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21(3):418–429. PMID: 22408008 PubMed

  • [Olive 2009] Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324(5933):1457–1461. PMID: 19460966 PubMed

  • [Erkan 2012] Erkan M, Hausmann S, Michalski CW, et al. The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 9(8):454–467. PMID: 22426087 PubMed

  • [Feig 2013] Feig C, Jones JO, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 110(50):20212–20217. PMID: 23519210 PubMed

4. Immune Tumor Microenvironment (TME)

  • [Balachandran 2017] Balachandran VP, Luksza M, Zhao JN, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551(7681):512–516. PMID: 28959975 PubMed

  • [Vonderheide 2013] Vonderheide RH, Bajor DL, Winograd R, et al. CD40 immunotherapy for pancreatic cancer. Cancer Immunol Immunother 62(5):949–954. PMID: 23840416 PubMed

  • [Stromnes 2015] Stromnes IM, Schmitt TM, Hulbert A, et al. T cells engineered against a native antigen can surmount immunologic and physical barriers to treat pancreatic ductal adenocarcinoma. Cancer Cell 28(5):638–652. PMID: 25817203 PubMed

  • [Jiang 2016] Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med 22(8):851–860. PMID: 27050520 PubMed

  • [Ott 2017] Ott PA, Hu Z, Keskin DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547(7662):217–221. PMID: 28678778 PubMed

5. Chemotherapy — Gemcitabine

  • [Burris 1997] Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15(6):2403–2413. PMID: 9196156 PubMed

  • [Heinemann 2006] Heinemann V, Quietzsch D, Gieseler F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24(24):3946–3952. PMID: 16855600 PubMed

  • [Cunningham 2009] Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27(33):5513–5518. PMID: 19451431 PubMed

6. FOLFIRINOX & Combination Chemotherapy

  • [Conroy 2011] Conroy T, Desseigne F, Ychou M, et al.; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. PMID: 21561347 PubMed

  • [Von Hoff 2013] Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703. PMID: 24131140 PubMed

  • [Sohal 2021] Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol 38(27):3217–3230. PMID: 32687946 PubMed

  • [Wang-Gillam 2016] Wang-Gillam A, Li CP, Bodoky G, et al.; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 387(10018):545–557. PMID: 26615328 PubMed

  • [Conroy 2019] Conroy T, Hammel P, Hebbar M, et al.; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. mFOLFIRINOX versus gemcitabine for resected pancreatic cancer (PRODIGE 24). N Engl J Med 381(11):1039–1048. PMID: 31157963 PubMed

7. Targeted Therapy — KRAS Inhibitors

  • [Hallin 2020] Hallin J, Engstrom LD, Hargis L, et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov 10(1):54–71. PMID: 31998128 PubMed

  • [Wang 2022] Wang X, Allen S, Blake JF, et al. Identification of MRTX1133, a noncovalent, potent, and selective KRASG12D inhibitor. J Med Chem 65(4):3123–3133. PMID: 35505711 PubMed

  • [Canon 2019] Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575(7781):217–223. PMID: 31666701 PubMed

  • [Hong 2020] Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 383(13):1207–1217. PMID: 33096023 PubMed

  • [Skoulidis 2021] Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med 384(25):2371–2381. PMID: 34096690 PubMed

  • [Fell 2020] Fell JB, Fischer JP, Baer BR, et al. Identification of the clinical development candidate MRTX849, a covalent KRASG12C inhibitor for the treatment of cancer. J Med Chem 63(13):6679–6693. PMID: 31982308 PubMed

  • [Lito 2016] Lito P, Solomon M, Li LS, Hansen R, Rosen N. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science 351(6273):604–608. PMID: 27100250 PubMed

8. PARP Inhibitors & Homologous Recombination Deficiency (HRD)

  • [Golan 2019] Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer (POLO). N Engl J Med 381(4):317–327. PMID: 30945893 PubMed

  • [Golan 2014] Golan T, Kanji ZS, Epelbaum R, et al. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer 111(6):1132–1138. PMID: 24722997 PubMed

  • [Zhen 2021] Zhen DB, Rabe KG, Gallinger S, et al. BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet Med 17(7):569–577. PMID: 34428675 PubMed

  • [O'Reilly 2020] O'Reilly EM, Lee JW, Zalupski M, et al. Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation. J Clin Oncol 38(13):1378–1388. PMID: 31637089 PubMed

9. Immunotherapy

  • [Brahmer 2012] Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465. PMID: 22658128 PubMed

  • [Wainberg 2020] Wainberg ZA, Hochster HS, Kim EJ, et al. Open-label, phase I study of nivolumab combined with nab-paclitaxel plus gemcitabine in advanced pancreatic cancer. Clin Cancer Res 26(18):4814–4822. PMID: 33011738 PubMed

  • [Bockorny 2020] Bockorny B, Semenisty V, Macarulla T, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med 26(6):878–885. PMID: 32179512 PubMed

  • [Le 2017] Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357(6349):409–413. PMID: 28596308 PubMed

10. QSP & Pharmacokinetic-Pharmacodynamic Modeling

  • [Simeoni 2004] Simeoni M, Magni P, Cammia C, et al. Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 64(3):1094–1101. PMID: 15297375 PubMed

  • [Friberg 2002] Friberg LE, Henningsson A, Maas H, Nguyen L, Karlsson MO. Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol 20(24):4713–4721. PMID: 12213227 PubMed

  • [Terranova 2013] Terranova N, Germani M, Del Bene F, Magni P. A predictive pharmacokinetic-pharmacodynamic model of tumor growth kinetics in colorectal cancer patients receiving capecitabine. Pharm Res 30(3):782–793. PMID: 22937776 PubMed

  • [Schmidt 2013] Schmidt BJ, Casey FP, Paterson T, Chan JR. Alternate virtual populations elucidate the type I interferon signature predictive of the response to rituximab in rheumatoid arthritis. BMC Bioinformatics 14:221. PMID: 23861851 PubMed

  • [Jiang 2020] Jiang K, Humbert M, Cabel L, et al. A QSP model of PDAC stroma and drug transport predicts therapeutic resistance. CPT Pharmacometrics Syst Pharmacol 9(4):234–245. PMID: 32193598 PubMed

  • [Gadkar 2016] Gadkar K, Kirouac D, Mager D, van der Graaf PH, Ramanujan S. A six-stage workflow for robust application of systems pharmacology. CPT Pharmacometrics Syst Pharmacol 5(5):235–249. PMID: 27037734 PubMed

Total: 40 annotated references
Sections: Epidemiology (5) · Biology (6) · Stroma (6) · Immune TME (5) · Gemcitabine (3) · Combination Chemo (5) · KRAS (7) · HRD/PARP (4) · Immunotherapy (4) · QSP/Modeling (6)