Pancreatic Cancer: Research Update

Pancreatic cancer is an aggressive form of human cancer with a high mortality rate, so patients need to be proactive. In this page, I will first review the conventional approach to pancreatic cancer  (Section A) and follow up with a brief examination of  a few causes and mechanisms that can make this type of cancer lethal (Section B).

Section A

Pancreatic ductal adenocarcinoma (PDAC), as the most frequent form of pancreatic malignancy, still is associated with a dismal prognosis. Due to its late detection, most patients are ineligible for surgery, and chemotherapeutic options are limited. Tumor heterogeneity and a characteristic structure with crosstalk between the cancer/malignant cells and an abundant tumor microenvironment (TME) make PDAC a very challenging puzzle to solve. Thus far, targeted therapies have failed to substantially improve the overall survival of PDAC patients.

Pancreatic cancer represents the fourth leading cause of cancer death in United States. More than 43,000 people are diagnosed with pancreatic cancer each year and about the same number die each year from the disease. Only about 3% of people with pancreatic cancer live more than five years after diagnosis. There are several reasons why mainstream oncology has not been succcessful with this type of cancer. First pancreatic cancer is aggressive, meaning its cancer cells are poorly differentiated. As a result,  it’s  quicker to metastasize or spread to other parts of the body. Another reason why this malignancy is difficult is because at first it’s asymptomatic, thus before symptoms surface, it is usually in an advanced stage. Furthermore, pancreatic cancer responds very poorly to current chemotherapy and radiation treatments, worse than other cancers. And lastly, not enough holistic science is applied.

Pancreatic Cancer is difficult to Diagnose in its early stages

Pancreatic cancer is hard to diagnose because the early symptoms are usually vague. Early symptoms are usually nothing more than a general feeling of discomfort in the abdomen or an unexplained weight loss. Jaundice, which occurs when the growing tumor blocks the bile duct, is often the symptom that first causes patients to go to their doctor.

The pancreas is a small organ located in the back of the abdomen and surrounded by the stomach, large intestine and liver. This makes it hard to see the pancreas with imaging technologies and difficult to access to remove cells for a biopsy. Even at a small size, cancer originating in the pancreas spreads quickly to other organs

Work-up

Physical examination. The doctor will examine the skin, tongue, and eyes to see if they are yellow, which is a sign of jaundice. Jaundice can be from a tumor in the head of the pancreas blocking the normal flow of a substance produced in the liver called bile. However, many patients with pancreatic cancer do not have jaundice when the cancer is diagnosed. Your doctor will also feel your abdomen for changes caused by the cancer, although the pancreas itself, located in the back of the upper abdomen, can rarely be felt. An abnormal buildup of fluid in the abdomen, called ascites, may be another sign of cancer.

Blood tests. The doctor may take samples of blood to check for abnormal levels of bilirubin and other substances. Bilirubin is a chemical that may reach high levels in patients with pancreatic cancer due to blockage of the common bile duct by a tumor. There are many other non-cancerous causes of an elevated bilirubin level, such as hepatitis, gallstones, or mononucleosis.

Carbohydrate antigen 19-9 (CA19-9) is a tumor marker. A tumor marker is a substance produced by a tumor that may be found at higher levels if cancer is present and can be measured in the blood. CA19-9 levels are often increased in people with pancreatic cancer, although some patients have normal CA19-9 levels. CA19-9 levels often become higher as the cancer grows or spreads. CA 19-9 should not be used as the only test to diagnose pancreatic cancer because high levels of CA 19-9 also can be a sign of other conditions. For example, other types of cancer, such as colorectal, liver, and esophageal cancers can increase CA 19-9. And noncancerous conditions, such as pancreatitis, cirrhosis of the liver, and a non-cancerous blockage of the common bile duct may also increase CA 1

 Maintream Oncology’s Limitations

For now, the only FDA-approved mainstream therapies for PC are gemcitabine and erlotinib, both of which produce objective responses in less than 10% of patients, while causing severe side-effects in the majority. (1) (Source)

There is thus an urgent need for new options (See clinical trials) and holistic solutions (see blog).

Section B

Causation and Mechanisms

Cancer Stem Cells: one of the key Mechanisms that is still under-estimated

In 2007, cancer scientists  identified a small group of cells, called cancer stem cells, in tumors from patients with pancreatic cancer. Researchers believe these stem cells are the key to finding an effective treatment and possibly someday a cure for pancreatic cancer.

Researchers have shown that just a few cancer stem cells are responsible for the growth and spread of pancreatic cancer. Unless these stem cells are removed or dedifferentiated back into normal cells, the cancer usually returns. Mainstream oncologists are working on devloping new drugs to target directly  cancer stem cells. To develop these drugs, scientists are looking for specific signaling pathways and cell surface markers found in cancer stem cells. Cancer stem cells are prognitor cells, meaning that they are the source of daughter cells and organize the malignancy. (2) (See blog on cancer stem cells).

Causes & Risks

Like many types of cancer, pancreatic cancer is caused by a combination of inherited genetic factors and environmental or lifestyle factors, from diet, smoking, to household toxins, stress and the like, all of which lead to a breakdown of homeostasis and the bioterrain. We know that at least 25% of all cases of pancreatic cancer are associated with smoking, including second hand.

There also are genetic links to pancreatic cancer. A family history of the disease is present in about 10% of all cases. There is a disproportionate amount of Jews who get diagnosed with this malignancy. Pancreatic cancer is associated with genetic mutations known to cause other types of cancer like melanoma, breast or colon cancer. Scientists still don’t know most of the gene alterations that increase a person’s susceptibility to pancreatic cancer.

In recent research, scientists have identified a gene called ATDC that appears to play a major role in this disease. They found that this gene was abnormally active in pancreatic tumor cells – causing tumors to grow faster and more aggressively in research mice, as well as making the cells resistant to chemotherapy.

“These results delineate a novel molecular pathway for EMT in pancreatic tumorigenesis, showing that ATDC is a proximal regulator of EMT.” (Source)

Other researchers have found that bacteria would be the decisive mechanism by which treatment resistance occurs. (See blog) And still other scientists have found that it’s the chemo and RT that cause metastases via cancer stem cell activation. (See blog article).

A few years ago,  dietary fat of animal origin was associated with increased pancreatic cancer risk.

“In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.” (3) (Source)

In a 2013 study, poultry was identified as a major culprit.  72% increased risk of pancreatic cancer for every 50g of daily poultry consumption. (Source) That’s like a quarter of a chicken breast. The reason white meat came out worse than red may be because of the cooked meat carcinogens in chicken, the heterocyclic amines that build up in grilled and baked chicken. These mutagenic chemicals have been associated with doubling pancreatic cancer risk. Furthermore, there’s been more evidence that  mainstream chicken contains arsenic. And arsenic is a big cancer driver.

Other recent studies include one out of San Francisco, implicating the standard American diet and one out of Italy: high consumption of meat and other animal products, as well as of refined carbs was associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables appeared to lower risk. *(4)  (Source)

While eating meat and processed junk foods and sugar has been shown to signficantly increase the risk of pancreatic cancer, eating a plant-based diet has been shown to be protective. Those who eat plant-based meats like veggie burgers or veggie dogs three times or more a week had less than half the risk of fatal pancreatic cancer. Legumes and dried fruit were found to be similarly protective.

Tentative conclusion: A diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated. (5) (Source)

Pancreatic Cancer does not respond well to Conventional Immunotherapy and Immune checkpoint Inhibition

Immune checkpoint inhibition, as an emerging therapeutic option in cancer treatment, shows promising results in different solid tumor types and hematological malignancies. However,  pancreatic cancer does not respond well to immune checkpoint inhibitors anti-programmed cell death protein 1 (PD-1) or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) alone or in combination. PDAC with its immune-privileged nature, starting from the early pre-neoplastic state, appears to escape from the antitumor immune response unlike other neoplastic entities. (Source)  Pancreatic cancer cells’ immunosuppressive TME (Tumor microenvironment) appears to be relevant.

Discussion

Since pancreatic cancer is resistant to chemotherapy, radiation and conventional immunotherapy, worse, because it has been shown that both cytotoxic chemotherapy and ionic radiation spur cancer stem cells to be stronger and more invasive,  new treatments are needed that can neutralize or redifferentiate the small number of cancer stem cells within the tumor, inter alia.

While there are a few alternative and holistic pathways that are interesting to explore, a patient can first and foremost remove some of the dietary causes that have been identified above. A while back, Harvard University also showed that there is a correlation between coffee and pancreatic cancer. Thus to be on the safe side, minimizing coffee, especially dark non organic coffee would be a reasonable lifestyle change. It’s not the coffee per se the problem, it’s the dark combustion, two residues of which are benzenes and tar, what exists in cigarettes.

Conclusion

While pancreatic cancer is a tough malignancy to reverse, hope and optimism should be associated with a reasonable plan of holistic action, if only because every now and then there are new discoveries on biochemical pathways, new findings with clinical trials, more pancreatic cancer patients showing  that it’s possible to reverse this disease holistically. The ACR Institute is organizing itself so that it will have the means to dig deep in order to find durable reversal solutions including with pancreatic cancer. In the Institute’s Holistic Immunotherapeutic Protocol, we have found interesting pathways that can target pancreatic cancer cells without collateral damage.  But we would need a clinical trial to prove that this approach is effective.

Meanwhile, patients can schedule coaching or consultation session in order to explore holistic reversal pathways that are not well known and that have been shown to be relatively safe and effective with solid cancers, including pancreatic malignancies. There are no guarantees, but the beauty of a holistic approach is that there is few if any side effects, on the contrary, most vital organs are enhanced. So at best, if ACR Institute’s holistic approach is not enough to reverse a terminal pancreatic cancer, it may prolong lifespan and strengthen quality of life.

Pr. J. (ACRI director)

Text still under construction

Reference and Precision Notes

(1). Z Y Yang, J Q Yuan, M Y Di, D Y Zheng, J Z Chen, H Ding, X Y Wu, Y F Huang, C Mao, J L Tang. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. PLoS One. 2013;8(3):e57528.
(2). Pancreatic cancer stem cells can be identified by the presence of three protein surface markers called CD44, CD24 and ESA. Recent work suggests that c-Met is another important marker on the cell surface of cancer cells. Other cells in pancreatic tumors don’t have this combination of protein markers. These surface proteins help pancreatic cancer stem cells stick to other cell surfaces. They also trigger important signaling pathways between stem cells and their environment. Only 0.5% to 1% of cells from pancreatic tumors contained the unique cancer stem cell fingerprint of three protein surface markers called CD44, CD24 and ESA. Regardless of the organ in which they are found, cancer stem cells appear to be responsible for the propagation of cancer and for its spread to other organs in the body. But they may do this in different ways. While many cancer stem cells may have one or two protein surface markers in common, scientists have not identified a universal fingerprint for all cancer stem cells. Scientists still don’t know if all cancer stem cells use the same signaling pathways to drive the development of cancer.
(3). A C Thiébaut, L Jiao, D T Silverman, A J Cross, F E Thompson, A F Subar, A R Hollenbeck, A Schatzkin, R Z Stolzenberg-Solomon. Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. J Natl Cancer Inst. 2009 Jul 15;101(14):1001-11.
(4)  J M Chan, Z Gong, E A Holly, P M Bracci. Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Nutr Cancer. 2013;65(1):157-64.
(5). C Bosetti, F Bravi, F Turati, V Edefonti, J Polesel, A Decarli, E Negri, R Talamini, S Franceschi, C La Vecchia, M P Zeegers. Nutrient-based dietary patterns and pancreatic cancer risk. Ann Epidemiol. 2013 Mar;23(3):124-8.

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Disclaimer: Nothing in this educational blog should be construed as medical advise.
2016 (c). Advanced Cancer Research Institute and agents. All Rights Reserved

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