From famous actors like Patrick Swayze to America's first woman in space, Sally Ride, the survival rates for pancreatic cancer summarizes grim tales. To date, the overall 5-year-survival rate is 6.7%. Here, I present some of the latest information in the field.
2. Outline
Description
• Epidemiology
• Risk factors
• Tumor types
• Prognosis of different tumor types
• Mutation frequencies in patients
• Potential biomarkers & diagnosis
• Guidelines for treatment
• Investigational & approved drugs
3. Description
Epidemiology, risk factors (1,2) and tumor types (3)
43,538 pancreatic cancer pts in the USA
(1)
Anticipated to become the 2nd-leading
cause of cancer deaths by 2020
Tumor types (3)
Non-endocrine (Adenocarcinoma):
> 75%
Endocrine (glucagonamas &
insulinomas): 1%
Non-endocrine (Other): ~24%
4th leading
cause of
cancer
deaths in
the USA
5-year
survival
rate (2004-
2010) (1)
6.7%
Pancreatic Adenocarcinoma (85% of all
pancreatic cancers); median age = 71 years (2)
Risk factors: smoking, long-standing DM, non-hereditary
& chronic pancreatitis,
obesity/inactivity/both, non-O blood group (2)
1. Surveillance, Epidemiology and End Results (SEER) program website (A service of the surveillance research program at the National Cancer Institute, USA): SEER Stat Fact Sheets. Pancreas Cancer
2. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. NEJM 2014;371(11):1039-49.
3. Johns Hopkins University School of Medicine (The Sol Goldman Pancreatic Cancer Research Center): Types of Pancreas Tumors 2014
http://pathology.jhu.edu/pc/BasicTypes2.php?area=ba
4. Prognosis of different tumor types
(A) Dire and (B) Potentially curable; Johns Hopkins University(1)
1. Endocrine tumors 6. Giant cell tumors
2. Adenocarcinoma 7. Mucinous Cystic Neoplasms
3. Acinar cell carcinoma 8. Pancreatoblastoma
4. Adenosquamous carcinoma 9. Signet Ring Cell Carcinoma
5. Colloid carcinoma 10. Undifferentiated tumors
• (A) Dire prognosis
1. Intraductal papillary mucinous neoplasm
2. Serious cystadenomas
3. Solid and pseudopapillary tumors
• (B) Potentially curable
3. Johns Hopkins University School of Medicine (The Sol Goldman Pancreatic Cancer Research Center): Types of Pancreas Tumors 2014 [cited 2014 September]. Available from: http://pathology.
5. ~Mutation frequencies in patients
Commonly mutated oncogenes & tumor suppressors
PADC
• KRAS (>90%)
• P53 (60-70%)
• CDKN2A (>50%)
• SMAD4, TGF-βR1,
TGF-βR2 (50%)
• ARID1A, ARID1B,
SMARCA1 (10-15%)
• MLL2, MLL3, KDM6A
(5-10%)
• ATM, BRCA2 (10%)
IPMNC
• GNAS (40-80%)
• KRAS (40-65%)
• RNF43 (>50%)
Oncogenes
Tumor
suppressors
ARID1A, AT-rich interactive domain 1A; ARID1B, AT-rich interactive domain 1B; ATM ataxia telangiectasia–mutated;
CDKN2A cyclin-dependent kinase inhibitor 2A; GNAS guanine nucleotide binding protein, alpha stimulating;
GPCR G-protein–coupled receptor; IPMNC, intra-papillary mucinous neoplasms;
KDM6A lysine (K)-specific demethylase 6A; KRAS Kirsten rat sarcoma viral oncogene homologue;
MLL2 mixed-lineage leukemia 2; MLL3 mixed-lineage leukemia 3; PADC, pancreatic ductal adenocarcinoma; RNF43
ring-finger protein 43; SMAD4 SMAD family member 4; SMARCA1 SWI/SNF-related, matrix-associated,
actin-dependent regulator of chromatin, subfamily a, member 1; TGF-β transforming growth factor β; TGF-βR1, TGF-β receptor
1; and TGF-βR2 TGF-β receptor 2
*Tumors with intact or deleted SMAD4 associated with different disease features
2. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. NEJM. 2014;371(11):1039-49.
6. Potential biomarkers* & diagnosis
NCCN-recommended tests (4)
Investigational biomarkers
in addition to CA19.9
• Aberrantly methylated DNA
(5)
• miR-205, miR-210, miR-492,
and miR-1427 & serum CA19-
9 levels (6)
• Serum peptide signatures (7)
• CA125, CA19.9 and LAMC2 (8)
CT, computed tomography; EUS, endoscopic ultrasound; ERCP, endoscopic retrograpde cholangiopancreatography; MRI, magnetic resonance imaging; MRCP, magnetic
cholangiopancreatography, miR is microRNA
4. National Comprehensive Cancer Network Guidelines for Patients v1.2014 (Pancreatic Cancer) http://www.nccn.org/patients/guidelines/pancreatic/#1.
5. Zhao Y, Sun J, Zhang H, et al. High-frequency aberrantly methylated targets in pancreatic adenocarcinoma identified via global DNA methylation analysis using methylCap-seq.
Clinical Epigenetics. 2014;6(1):18.
6. Wang J, Raimondo M, Guha S, et al. Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer.
Journal of Cancer. 2014;5(8):696-705.
7. Velstra B, Vonk MA, Bonsing BA, et al. Serum peptide signatures for pancreatic cancer based on mass spectrometry: a comparison to CA19-9
levels and routine imaging techniques. Journal of Cancer Research and Clinical Oncology. 2014.
8. Chan A, Prassas I, Dimitromanolakis A, et al. Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer.
Clinical cancer research. 2014.
7. Guidelines for treatment
NCCN (4)
Treatment order
Neoadjuvant Primary Adjuvant 2nd-line
Treatment type
Resectable Tumors not removable by
surgery are unresectable
3D-CRT, three-dimensional conformal radiation therapy; IMRT, intensity-modulated radiation therapy; SABR, stereotactic ablative radiotherapy
4. National Comprehensive Cancer Network Guidelines for Patients v1.2014 (Pancreatic Cancer) http://www.nccn.org/patients/guidelines/pancreatic/#1.
8. Investigational & approved drugs
Pancreatic cancer market 2014
Reprogramming of
tumor stroma with the
VDR-ligand, calcipotriol,
may enhance therapy
(pre-clinical)9,
Targeted therapies*
Immunotherapies*
Chemotherapies*
VDR, vitamin-D-receptor
9. Sherman MH, Yu RT, Engle DD, Ding N, et al. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic
cancer therapy. Cell. 2014;159(1):80-93.
