The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Pancreatic cancer: why is it so hard to treat?
Open accessAbstract
No common malignancy is as rapidly and inevitably fatal as pancreatic ductal adenocarcinoma (PDA). This grim fact has driven substantial research efforts into this disease in recent decades. Unfortunately, the investment has yet to result in a meaningful increase in 5-year survival. This has prompted many pancreatic cancer researchers and advocates to redouble their efforts, but also requires one to step back and ask why the previous efforts were lacking and to consider why pancreatic cancer is so difficult to treat. The difficulties are legion. PDA is characterized by an insidious clinical syndrome, but is rarely diagnosed at a time when surgical resection is feasible. We lack markers of early detection and screening programs remain unproven even in high risk populations. The location of the tumor in the retroperitoneum, the advanced age of patients, and the systemic effects of disease limit the options for local therapy. Chemotherapy may provide a small benefit, but most efforts to improve on the current regimens consistently and stubbornly fail in advanced clinical trials. The molecular and cellular features of ductal pancreatic tumors are aggressive and underlay multiple levels of therapeutic resistance. Non-cell-autonomous features including stromal proliferation, reduced vascular density and immune suppression also contribute to therapeutic resistance. Growing awareness of these the fundamental features of PDA has begun to guide ongoing research efforts. Clinical trials are now specifically targeting these tumor properties and actively focusing on the therapeutic implications of tumor stroma. As reviewed here, reflecting on the fundamental question of why pancreatic cancer is so difficult to treat is a necessary and informative exercise that will aid our efforts to improve patient outcomes. These efforts will lead to improvements in clinical trial design, expand our focus to include the molecular and histologic implications of novel treatment paradigms, and ultimately change the lives of our patients.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810
Moore, M. J., Goldstein, D., Hamm, J., Figer, A., Hecht, J. R., Gallinger, S., Au, H. J., Murawa, P., Walde, D., Wolff, R. A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9525 · Cited by 3,848
Distant metastasis occurs late during the genetic evolution of pancreatic cancer
Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., et al. (2010) · Nature · doi:10.1038/nature09515 · Cited by 2,502
DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1
Hahn, S. A., Schutte, M., Shamsul Hoque, A. T. M., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., et al. (1996) · Science · doi:10.1126/science.271.5247.350 · Cited by 2,337
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058 · cited 1×
“Besides these well-established ‘driver’ variations, many other genetic changes occur at lower frequencies [Hansel et al. 2003; Jones et al. 2008; Biankin et al. 2012; Perez-Mancera et al. 2012].”
BackgroundOncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome
Olive, K. P., Tuveson, D. A., Ruhe, Z. C., Yin, B., Willis, N. A., Bronson, R. T., Crowley, D., & Jacks, T. (2004) · Cell · doi:10.1016/j.cell.2004.11.004 · Cited by 1,308
Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947 · cited 2×
“Following activation, the principle upregulated cytokine is granulocyte-macrophage colonystimulating factor (GM-CSF), which was found to promote the recruitment and activation of immature myeloid progenitor cells to become myeloid derived suppressor cells [Bayne et al. 2012; Pylayeva-Gupta et al. 2012].”
BackgroundCellular pharmacology of gemcitabine
Mini, E., Nobili, S., Caciagli, B., Landini, I., & Mazzei, T. (2006) · Annals of Oncology · doi:10.1093/annonc/mdj941 · Cited by 842
Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice
Collins, M. A., Bednar, F., Zhang, Y., Brisset, J.-C., Galbán, S., Galbán, C. J., Rakshit, S., Flannagan, K. S., Adsay, N. V., & Pasca di Magliano, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59227 · Cited by 770
Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia
Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G., & Bar-Sagi, D. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.024 · Cited by 721
Maitra, A., & Hruban, R. H. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154305 · Cited by 707
The role of stroma in pancreatic cancer: Diagnostic and therapeutic implications
Erkan, M., Hausmann, S., Michalski, C. W., Fingerle, A. A., Dobritz, M., Kleeff, J., & Friess, H. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.115 · Cited by 662
Frequent detection of pancreatic lesions in asymptomatic high-risk individuals
Canto, M. I., Hruban, R. H., Fishman, E. K., Kamel, I. R., Schulick, R., Zhang, Z., Topazian, M., Takahashi, N., Fletcher, J., Petersen, G., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.01.005 · Cited by 648 · cited 2×
“Studies are ongoing in targeted populations of patients at high risk [Langer et al. 2009; Verna et al. 2010; Canto et al. 2012].”
BackgroundYachida, S., White, C. M., Naito, Y., Zhong, Y., Brosnan, J. A., Macgregor-Das, A. M., Morgan, R. A., Saunders, T., Laheru, D. A., Herman, J. M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1215 · Cited by 280
Molecular markers of early pancreatic cancer
Goggins, M. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.19.711 · Cited by 214
Molecular pathogenesis of pancreatic cancer
Hansel, D. E., Kern, S. E., & Hruban, R. H. (2003) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.4.070802.110341 · Cited by 159
Hruban, R. H., Petersen, G. M., Goggins, M., Tersmette, A. C., Offerhaus, G. J. A., Falatko, F., Yeo, C. J., & Kern, S. E. (1999) · Annals of Oncology · doi:10.1093/annonc/10.suppl_4.s69 · Cited by 134
Cited by
Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors
Rawla, P., Sunkara, T., & Gaduputi, V. (2019) · World Journal of Oncology · doi:10.14740/wjon1166 · Cited by 2,269
Mukhopadhyay, S., Goswami, D., Adiseshaiah, P. P., Burgan, W., Yi, M., Guerin, T. M., Kozlov, S. V., Nissley, D. V., & McCormick, F. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-1363 · Cited by 279
Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes
Maurer, C., Holmstrom, S. R., He, J., Laise, P., Su, T., Ahmed, A., Hibshoosh, H., Chabot, J. A., Oberstein, P. E., Sepulveda, A. R., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317706 · Cited by 216
Self-citationCurrent and Emerging Therapies in Metastatic Pancreatic Cancer
Manji, G. A., Olive, K. P., Saenger, Y. M., & Oberstein, P. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2319 · Cited by 145
iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery
Kang, S., Lee, S., & Park, S. (2020) · Polymers · doi:10.3390/polym12091906 · Cited by 139
Metadata
- Authors
- Oberstein, P. E., & Olive, K. P.
- Venue
- Therapeutic Advances in Gastroenterology
- Publisher
- SAGE Publications
- Published
- 2013-03-07
- Volume
- 6
- Issue
- 4
- Pages
- 321-337
- ISSN
- 1756-283X (ISSN-L)
- 1756-2848
- OpenAlex
- W2102509488
- Cited by
- 340
- References
- 19
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
