pancreatic ductal adenocarcinoma

1. Pancreatic ductal
adenocarcinoma
Ahmad Adel
59695

2. Its carcinoma that arise from the pancreatic ducts.
Pancreatic ductal
adenocarcinoma

3. • (PDA) is the fourth leading cause of cancer-related deaths in the
United States.
• (PDAC), constitutes over 90% of pancreatic cancers in humans.
• rapidly lethal: overall 5-year survival for PDA is less than 5%, with
a median survival of 4–6 months.

4. Etiology of the pancreatic ductal
adenocarcinoma
• Doctors have identified factors, that increase the risk of
developing the disease.
• Chronic inflammation of the pancreas (pancreatitis)
• Diabetes
• Family history of genetic syndromes that can increase cancer
risk, including a BRCA2 gene mutation and Lynch syndrome .

5. Factors that may increase your risk of
pancreatic cancer include:
• Family history of pancreatic cancer
• Smoking
• Obesity
• Older age, as most people are diagnosed after age 65
• A large study demonstrated that the combination of smoking, long-
standing diabetes and a poor diet increases the risk of pancreatic
cancer beyond the risk of any one of these factors alone.

6. Incidence of the pancreatic
ductal adenocarcinoma
The American Cancer Society’s estimates for pancreatic cancer
in the United States for 2018 are:
• Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all
cancer deaths.
• About 44,330 people (23,020 men and 21,310 women) will die of pancreatic cancer.
• About 55,440 people (29,200 men and 26,240 women) will be diagnosed with
pancreatic cancer.

7. This figure displays the correlation
between age and proportion of cases.

8. Clinical Presentation- Signs and
Symptoms
• Weakness/fatigue (asthenia)—86%
• Loss of appetite (anorexia)—85%
• Weight loss—85%
• Abdominal pain—79%
• Dark urine—59%

9. • Nausea—51%
• Back pain—49%
• Diarrhea—44%
• Vomiting—33%

10. Prognosis

11. Stage 1
• the cancer is not more than 4 cm in size

12. Stage 2
• the cancer has started to spread beyond the pancreas into
surrounding tissues or nearby lymph nodes.

13. Stage 3
• is called locally advanced cancer

14. Stage 4
• stage 4 means that the cancer has spread to other areas of the
body, such as the liver or lungs.

15. Molecular Abnormalities
Genomic (DNA) Alterations
• 1-Nuclear DNA Mutations: Oncogenes
• Activating point mutations within the KRAS oncogene (12p12.1)
,are present in 80 to 90% of pancreatic cancers,

16. 2-Tumor Suppressor Genes
• The cyclin-dependent kinase (CDKN2A/p16) on chromosome 9p
. inhibits cell cycle progression through the G1-S
checkpoint.
• More than 90% of pancreatic cancers show loss of CDKN2A/p16
function, which can occur due to homozygous deletions or
epigenetic silencing.

17. • Deletion in pancreatic carcinoma 4 (DPC4/SMAD4/MADH4) on
chromosome 18q21 in about 55% of pancreatic leads to
Loss of function
and results in
1. reduced growth inhibition.
2. increased proliferation.

18. 3-Caretaker Genes
• Caretaker genes minimize genetic alterations during DNA
replication so that loss of their function can lead to
accumulation of additional mutations in different other genes.
• Moreover, a subgroup of pancreatic cancers carries mutations in
genes of the Fanconi's anemia DNA repair pathway. Mutations
affecting the BRCA2 gene have been found in approximately 17%
of familial pancreatic cancers

19. Medical diagnosis of (PDA)
• Routine blood test e.g. liver products
Elevated tumor markers (CA 19-9 or CEA)
• MRI, CT scans and ultrasound
• Laparoscopy
• biopsy

20. • Endoscopy

21. Molecular diagnosis methods:
1-(allelotyping):
technique that is commonly applied to identify regions of genomic
losses at a “higher resolution” by means of polymorphic
microsatellite markers .
2-Comparative genomic hybridization (CGH)
used to discover genomic deletions as well as amplifications,
providing the potential to uncover both potential tumor
suppressor genes and oncogenes.

22. Medical treatment of the pancreatic
ductal carcinoma
• • Surgery
• • Chemotherapy
• • Palliation

23. molecular treatment
targeted cancer therapies
• are drugs or other substances that block the growth and spread
of cancer by interfering with ("molecular targets")
that are involved in the growth, progression, and spread of
cancer.

24. What types of targeted therapies are available?
• Signal transduction inhibitors block the activities of molecules
that participate in signal transduction.
• Gene expression modulators modify the function of proteins
that play a role in controlling gene expression.
• Apoptosis inducers cause cancer cells to undergo a process of
controlled cell death.

25. • The FDA has approved targeted therapies for several types of
cancer .
• Pancreatic cancer: Erlotinib (Tarceva®).
• everolimus (Afinitor®).
• sunitinib (Sutent®)

26. Thank you