Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) 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. https://doi.org/10.1158/0008-5472.CAN-14-0155

Article  CAS  PubMed  Google Scholar 

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21387

Article  PubMed  Google Scholar 

Li D, Xie K, Wolff R, Abbruzzese JL (2004) Pancreatic cancer. Lancet. 363(9414):1049–1057. https://doi.org/10.1016/S0140-6736(04)15841-8

Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C et al (2016) Pancreatic cancer: yesterday, today and tomorrow. Future Oncol 12(16):1929–1946. https://doi.org/10.2217/fon-2016-0010

Article  CAS  PubMed  Google Scholar 

National Cancer Institute at the National Institutes of Health (2020) Drugs Approved for Pancreatic Cancer. https://www.cancer.gov/about-cancer/treatment/drugs/pancreatic

Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR et al (1997) 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. https://doi.org/10.1200/jco.1997.15.6.2403

Article  CAS  PubMed  Google Scholar 

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. https://doi.org/10.1056/NEJMoa1011923

Article  CAS  PubMed  Google Scholar 

Jin J, Teng C, Li T (2018) Combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer: a meta-analysis of randomized controlled trials. Drug Des Devel Ther 12:475–480. https://doi.org/10.2147/DDDT.S156766

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25(15):1960–1966. https://doi.org/10.1200/JCO.2006.07.9525

Article  CAS  PubMed  Google Scholar 

Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C et al (2008) Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomized phase II study. Lancet 371(9630):2101–2108. https://doi.org/10.1016/S0140-6736(08)60661-3

Article  CAS  PubMed  Google Scholar 

Philip PA, Benedetti J, Corless CL, Wong R, O’Reilly EM, Flynn PJ et al (2010) Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 28(22):3605–3610. https://doi.org/10.1200/JCO.2009.25.7550

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kreso A, Dick JE (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14:275–291. https://doi.org/10.1016/j.stem.2014.02.006

Article  CAS  PubMed  Google Scholar 

Nassar D, Blanpain C (2016) Cancer Stem cells: Basic concepts and therapeutic implications. Annu Rev Pathol 11:47–76. https://doi.org/10.1146/annurev-pathol-012615-044438

Article  CAS  PubMed  Google Scholar 

Dean M, Fojo T, Bates S (2005) Tumor stem cells and drug resistance. Nat Rev Cancer 5:275–284. https://doi.org/10.1038/nrc1590

Article  CAS  PubMed  Google Scholar 

Hermann PC et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323. https://doi.org/10.1016/j.stem.2007.06.002

Article  CAS  PubMed  Google Scholar 

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013

Article  CAS  PubMed  Google Scholar 

Meacham CE, Morrison SJ (2013) Tumor heterogeneity and cancer cell plasticity. Nature 501:328–337. https://doi.org/10.1038/nature12624

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bivona TG et al (2011) FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR. Nature 471:523–526. https://doi.org/10.1038/nature09870

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seguin L et al (2014) An integrin beta(3)-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition. Nat Cell Biol 16:457–468. https://doi.org/10.1038/ncb2953

Article  CAS  PubMed  PubMed Central  Google Scholar 

Desgrosellier JS et al (2009) An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nat Med 15:1163–1169. https://doi.org/10.1038/nm.2009

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seguin L et al (2017) Galectin-3, a Druggable vulnerability for KRAS-Addicted cancers. Cancer Discov 7:1464–1479. https://doi.org/10.1158/2159-8290.CD-17-0539

Article  CAS  PubMed  PubMed Central  Google Scholar 

Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10:9–22. https://doi.org/10.1038/nrc2748

Article  CAS  PubMed  PubMed Central  Google Scholar 

Adhikari AS, Agarwal N, Iwakuma T (2011) Metastatic potential of tumor-initiating cells in solid tumors. Front Biosci 16:1927–1938

Article  CAS  Google Scholar 

Miller PG et al (2013) In vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 24:45–58. https://doi.org/10.1016/j.ccr.2013.05.004

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vaillant F et al (2008) The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammarytumorigenesis. Cancer Res 68:7711–7717. https://doi.org/10.1158/0008-5472.CAN-08-1949

Article  CAS  PubMed  Google Scholar 

Cheng J, Cashman JR (2020) Pancreatic cancer drug-sensitivity predicted by synergy of p53-Activator wnt Inhibitor-2 (PAWI-2) and protein biomarker expression. Investig New Drugs. https://doi.org/10.1007/s10637-020-00998-z

Article  Google Scholar 

Cashman JR, Mercola M, Schade D, Tsuda M (2013) Compounds for inhibition of cancer cell proliferation. Google Patents. 2013:US 13/748,70

Okolotowicz KJ, Dwyer M, Ryan D, Cheng J, Cashman EA, Moore S et al (2018) Novel tertiary sulfonamides as potent anti-cancer agents. Bioorg Med Chem 26(15):4441–4451. https://doi.org/10.1016/j.bmc.2018.07.042

Article  CAS  PubMed  Google Scholar 

Cheng J, Dwyer M, Okolotowicz KJ, Mercola M, Cashman JR (2018) A novel inhibitor targets both wnt Signaling and ATM/p53 in Colorectal Cancer. Cancer Res 78(17):5072–5083. https://doi.org/10.1158/0008-5472.CAN-17-2642

Article  CAS  PubMed  Google Scholar 

Cheng J, Okolotowicz KJ, Ryan D, Mose E, Lowy AM, Cashman JR (2019) Inhibition of invasive pancreatic cancer: restoring cell apoptosis by activating mitochondrial p53. Am J Cancer Res 9(2):390–405

CAS  PubMed