Advertisements
Feeds:
Posts
Comments

Posts Tagged ‘RGL2’


Author: Ritu Saxena, Ph.D.

Recently, two world renowned innovators, Steve Jobs-the CEO of Apple Inc. and Dr. Steinman-winner of 2011 Nobel prize in Physiology or medicine lost their life battle against Pancreatic cancer. Although both Jobs and Steinman suffered from the same disease, they were diagnosed with two fundamentally different forms of cancer of pancreas.

Steve lived with the disease for 8 years, a relatively long time for Pancreatic cancer patients to survive. The reason is attributed to the rare form of cancer of pancreas he suffered from-referred to as pancreatic neuroendocrine tumor. Steinman, on the other hand died due to a more common form of pancreatic cancer, the adenocarcenoma.

Neuroendocrine tumors arise from islands of hormone-producing cells (islets), that happen to be in that organ. Jobs learned in 2003 that he had an extremely rare form of this cancer, an islet-cell neuroendocrine tumor. In his email to  Apple employees in 2004, Steven Jobs wrote “I have some personal news that I need to share with you, and I wanted you to hear it directly from me,” Jobs said in the message, which he sent from his hospital bed. “I had a very rare form of pancreatic cancer called an islet cell neuroendocrine tumor, which represents about 1 percent of the total cases of pancreatic cancer diagnosed each year, and can be cured by surgical removal if diagnosed in time (mine was). I will not require any chemotherapy or radiation treatments.”

About 2,500 cases of pancreatic islet cell tumors are seen in the United States each year, according to the University of Southern California’s Center for Pancreatic and Biliary Diseases. These tumors, which are derived from neuroendocrine cells, tend to be slow growing and are treatable even after they have metastasized, said the center’s Web site.  http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2004/08/02/MNGMJ816F41.DTL&ao=all

The management strategy of neuroendrocrine tumors (NET) like any other disease is supposed to be curative where possible. As suggested by several researchers including Ramage et al (http://www.ncbi.nlm.nih.gov/pubmed/15686165, ), surgery is the only curative option currently available for NETs. The updated guidelines published for the NET management state the over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, because of the uncommon nature of the disease, there remain few randomised trials in the field, hence all evidence mentioned in the research article is considered relatively weak compared with other more common cancers. For patients who are diagnosed early enough to be candidates for surgery, the aim is to keep the patient disease- and symptom-free for as long as possible. For patients suffering from advanced-stage NETs, operative therapy is rarely curative and chemotherapy could be used on metastasized NETs. http://www.ncbi.nlm.nih.gov/pubmed/22052063.

As reported in a story covered by CNN in 2008, there was a lot of speculation when he appeared rail-thin at the unveiling of the new iPhone. Jobs eventually said in January 2009 that doctors said he dropped so much weight because of “a hormone imbalance that has been ‘robbing’ me of the proteins my body needs to be healthy. Sophisticated blood tests have confirmed this diagnosis.” http://tech.fortune.cnn.com/2008/06/13/steve-jobs-life-after-the-whipple/ This statement explains how symptoms of hormonal excess in NET patients must be controlled before surgical procedure is followed. Also, recommended management of the symptoms of hormonal hypersecretion depends on the hormone secreted. For example, glucose levels in patients with insulinomas should be stabilized with diet and/or diazoxide. Gastrin hypersecretion in patients with gastrinomas may be managed with proton pump inhibitors (PPIs). http://www.neuroendocrinetumor.com/health-care-professional/net-treatment-options.jsp

Steinman, on the other hand, suffered from adenocarcenoma that arises from the pancreatic cells themselves, referred to as the “far more common form of pancreatic cancer” by Jobs. He further wrote in his memo “…(adenocarcenoma) is currently not curable and usually carries a life expectancy of around one year after diagnosis. I mention this because when one hears ‘pancreatic cancer’ (or Googles it), one immediately encounters this far more common and deadly form, which, thank God, is not what I had.”

Dr. Steinman won the 2011 Nobel Prize for Medicine or Physiology for his early-career landmark discovery about the immune system in the 1970s when he first described ‘dendritic cells’ with the help of his mentor Zanvil Cohn at Rockefeller University. Unfortunately, he died just three days before the official announcement. http://www.scientificamerican.com/article.cfm?id=steinman-nobel-laureate-explains-discovery-dendritic-cells. He had been suffering from pancreatic cancer for four years, had been undergoing treatment using a pioneering immunotherapy based on his own research. Dendritic cells from his body were deployed to mount an assault on his cancer. His early research at Rockefeller, began as an attempt to understand the primary white cells of the immune system — the large “eating” macrophages and the exquisitely specific lymphocytes, which operate in a variety of ways to spot, apprehend and destroy infectious microorganisms and tumor cells. Steinman’s subsequent research pointed to dendritic cells as important and unique accessories in the onset of several immune responses, including clinically important situations such as rejection of graft, resistance to tumors, autoimmune diseases and infections including AIDS. http://newswire.rockefeller.edu/2011/10/03/rockefeller-university-scientist-ralph-steinman-honored-today-with-nobel-prize-for-discovery-of-dendritic-cells-dies-at-68/

The standard of care in the United States for the treatment of locally advanced pancreatic cancer is a combination of low-dose chemotherapy given simultaneously with radiation treatments to the pancreas and surrounding tissues. Radiation treatments are designed to lower the risk of local growth of the cancer, thereby minimizing the symptoms that local progression causes (back or belly pain, nausea, loss of appetite, intestinal blockage, jaundice). http://www.medicinenet.com/pancreatic_cancer/page6.htm#advanced

Research Efforts on Pancreatic Cancer: The untimely passing of the geniuses reminds us how important research in the area of pancreatic cancer is which lead to finding new therapeutic targets that might stem reliable therapies. A recent example is the report published in Science Daily stating that the protein RGL2 might be a promising therapeutic target for pancreatic cancer. http://www.sciencedaily.com/releases/2010/11/101105101400.htm. The conclusion was derived via research published in November in the Journal of Biological Chemistry by a team led by Channing Der, PhD from UNC Lineberger Cancer Center. http://www.jbc.org/content/285/45/34729.long   For almost three decades, scientists and physicians have known that a gene called the KRAS oncogene is mutated in virtually all pancreatic cancers, making it an important target for scientists looking for a way to stop the growth of pancreatic cancer tumors. The problem is that the KRAS gene triggers cancer cell growth in numerous ways, through multiple cell signaling pathways, and scientists have had difficulty determining which one will be the most promising to block — an important first step in designing a drug for use in patients. Dr. Der said that “We are particularly optimistic about RGL2 because we know that this protein is a critical component of KRAS signaling to another class of proteins called Ral GTPases, which are essential for the growth of almost all pancreatic tumors.”

Another groundbreaking research was published in the journal Nature talks about discovering the link between a gene and the prognosis of Pancreatic Ductal Adenocarcenoma. The team found that when a gene involved in protein degradation is switched-off through chemical tags on the DNA’s surface, pancreatic cancer cells are protected from the bodies’ natural cell death processes, become more aggressive, and can rapidly spread. Their research study proposed USP9X to be a major tumour suppressor gene with prognostic and therapeutic relevance in pancreatic cancer. http://www.sanger.ac.uk/about/press/2012/120429.html http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature11114.pdf

Although, most of the research efforts are concentrated on the more common form of cancer, pancreatic adenocarcenoma, similar research efforts are needed for developing cure for the uncommon form, the one Steve Jobs suffered from, neuroendocrine cancer.

What we lost to the disease is more than the two geniuses, we lost the possibility of further innovation that might have changed the world in ways we could not imagine. The loss, though, sheds light on the importance of finding a cure for the disease and its different types. Hope the research community is able to interpret and find answers to the enigma of Pancreatic cancer and its diverse forms in which it strikes.

Advertisements

Read Full Post »