Textbook of Personalized Medicine - Second Edition [2015]

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Personalized Management of Pancreatic Cancer


Pancreatic cancer is the fourth leading cause of death from cancer in the US;
approximately 95 % of those affected die from it. The lifetime risk of developing
pancreatic cancer is about 1 in 71. There are two types of pancreatic cancer: exo-
crine tumors and neuroendocrine tumors. Exocrine tumors are the majority of pan-
creatic cancers, and the most common form is an adenocarcinoma, which begin in
gland cells, usually in the ducts of the pancreas. These tumors tend to be more
aggressive than neuroendocrine tumors, but if detected early enough they can be
treated effectively with surgery. Neuroendocrine tumors constitute only 1 % of all
pancreatic cancers. They can be benign or malignant, but the distinction is often
unclear and sometimes apparent only when the cancer has spread beyond the pan-
creas. The 5-year survival rate for neuroendocrine tumors can range from 50 % to
80 %, compared with less than 5 % for adenocarcinoma. Pancreatic cancer is so
lethal because during the early stages, when it would be most treatable, there are
usually no symptoms. It tends to be discovered at advanced stages when abdominal
pain or jaundice may result. More advanced tumors have a higher risk of recurrence,
and can spread to the liver. Pancreatic cancer is usually controllable only through
removal by surgery, and only if found before it has spread. Palliative care can help
a patient’s quality of life if the disease has spread. The survival rate of pancreatic
cancer patients is the lowest among those with common solid tumors, and early
detection is one of the most feasible means of improving outcomes. Currently there
are no general screening tools.
Two drugs are approved for treatment of pancreatic neuroendocrine tumors:
everolimus (Novartis’ Afi nitor), and sunitinib malate (Pfi zer’s Sutent), which sup-
press angiogenesis and metabolism of the tumor cells. This is a progress compared
to previous standard of care, which was chemotherapy, but both these drugs can
have severe adverse effects. A number of new agents are being looked at in clinical
trials that focus on pathways involved in pancreatic cancer. One is an antibody in
development by NCI that blocks the protein PD-1 on the surface of pancreatic can-
cer, and would be more effective because it would produce an enhanced immune
response against the tumor. Targeted nanoparticles coated with material that hone in
on tumor cells and deliver drugs to kill them are being tested in animal models as
treatment for metastatic neuroendocrine tumors. The main advantage would be
reducing the toxicity of the drugs to the normal tissues of the body. The future treat-
ment of pancreatic cancer will involve a personalized approach, i.e. matching a
patient’s particular type of tumor with treatment using genomic information.


Biomarkers of Pancreatic Cancer


Unlike screenings for other conditions such as colon, breast and prostate cancers,
there is no routine way to see whether a patient has a tumor in the pancreas. Current
research is focused on fi nding biomarkers of pancreatic cancer so that a simple
blood or urine test could be developed. Because of the complex pathophysiology of


10 Personalized Therapy of Cancer
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