Pancreatic cancer - published scientific research

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In this thread I'd like to collate much of the info I've collected, read or researched in recent times. It will certainly assist someone who is about to learn more about this disease. I will leave a link and then I will cut and copy the bits I've found most interesting and enlightening. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684727/ Pancreatic Adenocarcinoma: New Strategies for Success Eileen M. O’Reilly GENETICS OF PANCREAS ADENOCARCINOMA It is estimated that approximately 10% of pancreatic cancers may be attributed to genetic factors.8–10 There are two major groups: the larger group is families with multiple individuals diagnosed with pancreas cancer but with no identifiable genetic defect; the smaller and more welldefined group includes recognizable genetic syndromes (Table 1).11 The importance of defining the genetics of this disease relates to the ultimate goals of identification of high-risk individuals, implementation of risk-reduction strategies, and decreasing mortality from this disease.12 Early data from the National Familial Pancreas Tumor Registry have demonstrated that healthy members of families that have two or more first-degree relatives with pancreas cancer have a 6.4-fold higher risk of developing the disease. This figure increases to a 32-fold higher risk if three or more first-degree relatives have the disease. Another key observation from these prospective registries is that not smoking reduces the risk of developing pancreatic cancer among these family members.13 Smoking cessation is a key public health measure and one potentially modifiable risk factor for this malignancy. Our pancreatic registry at Memorial Sloan-Kettering Cancer Center focuses on two groups of individuals: (1) Probands with pancreatic cancer diagnosed at less than 50 years of age, or with one or more first-degree relatives with pancreatic cancer, or two or more second-degree relatives with pancreatic cancer, or known BRCA-1 or BRCA-2 mutation; (2) the family member part of the registry is for individuals not diagnosed with pancreas cancer but with similar entry characteristics as for the proband group. Early registry findings have yielded the identification of two patients with adenocarcinomas following screening. Both patients subsequently underwent resection, including a 58-year-old female (T3,N0,M0) with two first-degree relatives, and a 46-year-old female (T3,Nx,M0) with one first-degree relative with pancreatic cancer. Other findings have included identification of one neuroendocrine cancer and four intraductal papillary mucinous neoplasms (IPMN). The latter observation raises the question of whether IPMNs might represent a precursor to adenocarcinoma in certain familial settings. Clearly, no conclusions can be drawn as these observations are preliminary—but enticing—with regard to identification of at-risk individuals. Consensus recommendations regarding who is at high risk and how to screen remain to be established. However, careful review of family history, particularly in families where pancreatic cancer occurs with breast, ovarian, other gastrointestinal cancers, or a history of pancreatitis, may identify at-risk families.14,15 These individuals should be considered for referral to a clinical genetics service and, if appropriate, undergo focused testing, eg, BRCA-2, etc, be counseled about smoking cessation, and ideally be enrolled on a prospective registry for early detection and screening.16 This also points to an emerging concept with potential future therapeutic application: A small but identifiable subset of patients (~ 7%) diagnosed with pancreatic cancer has a mutation in BRCA-2.8,17 Such patients may have greater susceptibility to DNA-damaging agents such as mitomycin or PARP (poly[ADP-ribose] polymerase) inhibitors.18 These latter drugs are coming to the clinic for pancreas cancer and information will evolve over the next couple of years. STATE-OF-THE-ART THERAPY FOR PANCREAS ADENOCARCINOMA 2008 Given that the vast majority of people with pancreatic cancer are diagnosed with locally advanced or metastatic disease, the major focus of drug development has been in the advanced and metastatic settings. Single-agent gemcitabine has been the default standard of care and has stood the test of a decade of challenge in this patient population. Data from Burris et al in 1997 demonstrated an improved clinical benefit (24% vs. 5%, P = .022), modest improvement in median survival (5.6 vs. 4.3 months, P = .0025), and significant increase in 1- year survival (18% vs. 2%) for gemcitabine compared with 5-fluorouracil in what may be one of the smallest randomized trials in any solid tumor to lead to drug approval by the U.S. Food and Drug Administration.19 Over the past decade, research aimed at improving outcomes in pancreatic cancer has focused on three groups of trials: comparing gemcitabine to other single agents (Table 2); combining gemcitabine with other cytotoxics (Table 3); and in the last 5 years, combining gemcitabine with newer targeted agents.20 For the most part, this has been a relatively disappointing series of ventures. In the first group of trials, other single agents have resulted in inferior outcomes compared with those achieved with gemcitabine, eg, exatecan mesylate (topoisomerase- I inhibitor),21 marimastat, and BAY 12-9566 (both matrix metalloproteinase inhibitors).22 These studies have indirectly re-endorsed the value of gemcitabine. Similarly, combinations of cytotoxic agents with gemcitabine, at least in individual trials, have not yielded improved outcomes, with the exception of a gemcitabine and capecitabine combination reported preliminarily from the Medical Research Council (MRC) group in the United Kingdom23; however, mature outcome data are awaited to confirm the value of this combination. Results of pooled analyses and metaanalyses have provided support for use of selected two-drug, gemcitabine-based combinations, particularly combined with a platinum agent, and to a lesser extent, combined with fluoropyrimidines.24,25 Median overall survival of pancreatic cancer patients treated with selected gemcitabine + drug “X” combinations compared with gemcitabine alone Another area of research that may have tangible clinical utility is pharmacogenomics as applied to standard cytotoxic agents that are active in pancreatic adenocarcinoma. Genetic polymorphisms, and tumor-specific expression of mRNA and proteins, may affect both the efficacy and toxicity of gemcitabine.26 For example, hENT1 (nucleoside transporter), RRM1 (rate-limiting step in DNA synthesis pathway), and DNA repair polymorphisms may have prognostic implications; low levels of the enzyme cytidine deaminase involved in the pyrimidine salvage pathway may confer toxicity. Examples for other drugs include dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) levels for 5-fluorouracil, and excision repair cross-complementation group 1 (ERCC-1) for oxaliplatin, which may confer information related to toxicity and sensitivity, respectively. Prospective pharmacogenomic- based biomarker studies are needed to define utility and identify patient subsets where therapy refinement is feasible. TARGETED THERAPY FOR PANCREATIC ADENOCARCINOMA The expectations and hope for the value of new biologic agents have, unfortunately, exceeded the reality of the challenges of pancreatic cancer. However, results of a randomized phase III trial comparing gemcitabine and erlotinib vs. gemcitabine in patients with untreated advanced disease provided a small but real hint of activity.27 A modest but statistically significant difference in median survival was noted, along with an improved progression-free survival (PFS) and a more compelling, approximate 40% improvement in 1-year survival (from 17% with gemcitabine to 23% with the combination). Moreover, there was an association between rash severity and survival in this trial, as has been observed in studies in other malignancies where anti-epidermal growth factor receptor (EGFR)-based therapies have had utility. Patients with rash grade ≥ 2 had a near-doubling of their survival to 10.5 months, compared with 5.3 months for patients with no rash. The challenge will be to identify the patients most likely to benefit from treatment in advance of a therapeutic trial. Information on molecular correlates was available from only approximately 21% (n = 117) of the study patients. There was a suggestion that patients with wild-type ras tumors may have had increased benefit from erlotinib; however, the small sample size limited the conclusions that could be made in this post-hoc K-ras mutational analysis.28 For now, the rash and ras story is evolving and there are no specific implications regarding patient care. In contrast to the data on gemcitabine combined with erlotinib, results of a phase III randomized trial comparing gemcitabine and cetuximab vs. gemcitabine in untreated, advanced pancreatic cancer patients have indicated no advantage with the addition of cetuximab (median survival, 5.4 months for the combination and 5.9 months for gemcitabine, hazard ratio [HR] 1.09).29 Of note, the absolute difference in survival for both erlotinib and cetuximab were similar at 0.5 months; however, one study was “positive” and the other “negative,” raising the question of whether there is a difference between a small molecule tyrosine kinase inhibitor and a monoclonal antibody in this disease. The anti-angiogenesis story is also unfolding in pancreatic cancer. Much promise was put upon an early phase II trial of gemcitabine and bevacizumab in a very select population of patients with untreated advanced disease.30 Unfortunately, results of a randomized phase III trial showed no improvement for the addition of bevacizumab to gemcitabine in a broader population of patients with advanced pancreatic cancer (median survival: gemcitabine, 6.1 months; gemcitabine and bevacizumab, 5.8 months; HR 10.3; P = .78).31 Axitinib, an oral vascular endothelial growth factor (VEGF) 1, 2, 3 inhibitor, which demonstrated promise in a small randomized phase II study,32 has completed phase III testing in advanced disease. A press release reported that the primary end point had not been met,33 and further details are awaited. A phase III study of gemcitabine +/− VEGFtrap (aflibercept) in patients with metastatic pancreatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 is ongoing. The AViTA study was the first trial to combine an anti-angiogenic and an anti-EGFR therapy in the phase III setting in pancreatic cancer.34 This trial evaluated the addition of bevacizumab to gemcitabine and erlotinib in patients with metastatic disease and ECOG performance status of 0–1. The study did not meet its primary end point: overall survival was 7.1 months vs. 6 months (P = .208) with vs. without bevacizumab, respectively; however, PFS improved significantly in the experimental arm, from 3.6 months without to 4.6 months with bevacizumab (P = .0002). Taken together, results of these trials suggest that the anti-angiogenesis story remains to be completely told in this disease. NEW DIRECTIONS Given the disappointments of the early era of targeted therapy in pancreatic cancer, the role of cytotoxics currently remains undiminished in this malignancy. Two new taxane derivatives are poised for phase III development. Nab-paclitaxel, a nanoparticle albumin-bound paclitaxel, has been combined with gemcitabine in an early phase I trial. Preliminary data, reported by Von Hoff et al,35 showed interesting activity with partial responses and Ca 19-9 biomarker decline in a significant number of patients, and with the suggestion that SPARC (secreted protein and rich in cysteine) might be a surrogate of poor outcome. A different method of paclitaxel delivery has been chosen for Endotag-1 formulation. Endotag-1 consists of cationic liposomes and paclitaxel. Proposed mechanisms of anti-tumor activity include endothelial cell and vascular disruption as well as cytotoxic activity. A randomized phase II study has explored several dosing schedules in untreated patients with both locally advanced and metastatic disease.36 Allowing for heterogeneity of the patient population, treatment duration, and dose levels, a suggestion of anti-tumor activity has been observed and further development is planned at this time. Other ongoing or imminently accruing phase III trials are summarized in Table 4. Additional areas of development of new therapeutics include insulin-like growth factor 1 receptor (IGF- 1R) signaling inhibitors combined with gemcitabine/erlotinib (Southwest Oncology Group [SWOG] phase II) and other kinase inhibitors,37 PI3/Akt signaling inhibition, PARP inhibition,18 c-Met inhibition, and antagonists of the tumor microenvironment, to name a few. Selected ongoing phase III trials in advanced pancreas cancer Much hope has been placed on the identification of mouse models for pancreatic adenocarcinoma that mimic the human condition with regard to morphology and clinical behavior, both significant limitations of earlier murine models of this disease. The access of a reliable in vivo model may provide opportunities, previously unavailable, for in vivo drug testing, and may be useful in identifying agents with a potential role in prevention of the disease.38 A preliminary analysis of 24 pancreatic genomes has provided further insights into the molecular biology and underpinnings of pancreatic cancer. Jones et al observed an average of 63 genetic alterations, mostly point mutations, in twelve major signaling pathways,5 many of which are being actively targeted by drugs in development. The hope here, however, is that clear directions for therapeutic development will come about with greater understanding of the onconeogenesis of this most challenging of human malignancies.39

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Emerging Molecular Biology of Pancreatic Cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661541/ Abstract Pancreatic cancer, like most other cancers, is fundamentally caused by mutations in specific genes. Many of the genes targeted in pancreatic cancer have been identified in the past decade, and an understanding of these genes and their function has helped identify familial forms of pancreatic cancer, define the precursor lesions from which invasive pancreatic cancers arise, and will soon lead to gene-specific therapies for this disease. This article reviews the tumor-suppressor genes, oncogenes, and DNA repair genes targeted in pancreatic cancer, and presents clinical applications based on our understanding of the genetic basis of pancreatic cancer.

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If you can not access full text PM me. Best Practice & Research Clinical Gastroenterology Volume 20, Issue 2, April 2006, Pages 227-251 Pancreatic Cancer Evidence-based diagnosis and staging of pancreatic cancer Only 20% of patients who present with pancreatic cancer will be amenable to potentially curative resection. Therefore, it is necessary to reliably identify patients who might benefit from major surgical intervention by employing the appropriate staging methods. In this review, the pros and cons of each imaging technique are discussed and an algorithm for single and combined use of the different imaging modalities is proposed. To date, contrast-enhanced multi-detector row helical CT (MDR-CT) together with endoscopic ultrasound (EUS) remain the first staging methods of choice. MDR-CT has a high sensitivity for identifying vascular invasion and EUS is able to detect lesions as small as 2–3 mm. ERCP is performed mainly in patients with biliary obstruction with the option for therapeutic intervention during the same session. MRI with MR-angiography, MRCP, PET/CT and staging laparoscopy are additional modalities which might give further information in cases of equivocal findings by MDR-CT and EUS. The role of tumour markers such as CA 19-9 and CEA is reserved for monitoring and diagnosing post-surgery recurrence. Cytological or histological confirmation should usually be performed in patients that are not eligible for surgery prior to the commencement of palliative radio- or chemotherapy. In the routine clinical setting, MDR-CT and EUS play the predominant roles by providing the most cost-effective and accurate means for diagnosing and staging most cases of pancreatic cancer. I've found that the most common component in staging or diagnosing PC or at least the most talked about component is "tumor markers" CA 19-9 and CEA are the tumor markers of concern, therefore I will leave a paragraph from this work about it; TUMOUR MARKERS In addition to imaging modalities, various laboratory tests are frequently being used for the diagnosis of pancreatic cancer as an adjunct to imaging techniques. A number of secreted proteins have been identified with increased serum levels in patients with pancreatic cancer. Apart from helping to diagnose the tumour, these tumour markers are thought to be useful for (i) indication of prognosis, (ii) assessment of therapeutic efficacy, and (iii) detection of residual or recurrent cancer.87 Carbohydrate antigen 19-9 (CA 19-9) is a glycoprotein expressed on the surface of pancreatic cancer cells as well as by normal human pancreatic and biliary duct cells. Increased levels of CA 19-9 are frequently found in the serum of patients with a variety of solid tumours such as pancreatic cancer, hepatocellular carcinoma, ovarian carcinoma, bronchial, colon and gastric cancers. Sensitivity of CA 19-9 for the detection of pancreatic cancer ranges in various studies from 67 to 92% with specificities ranging from 68 to 92%.88–91 A significant limitation of CA 19-9 is its insufficient sensitivity for small tumours: Only 50% of cancers !2 cm are associated Diagnosis of pancreatic cancer 241 with a rise in CA 19-9.92 In addition, patients with negative Lewis blood group antigen representing 4–15% of the population are unable to synthesize CA 19-9 and are therefore CA 19-9 negative for genetic reasons.93 Elevated CA 19-9 levels may also be found in patients with various cholestatic diseases,94 chronic pancreatitis and other types of inflammation.95 Only if high cut-off levels of CA 19-9 are taken, the specificity of this tumour marker rises over 90%,96 then however indicating extended disease. Other carbohydrate antigens measured in the serum include Carcinoembryonic antigen (CEA).97 CEA is normally expressed in normal mucosal cells and is overexpressed in gastrointestinal cancers, e.g. colorectal cancer and pancreatic cancer.98 However, elevated levels of CEA also occur in benign conditions such as inflammatory bowel disease, peptic ulcers, pancreatitis, biliary obstruction, as well as cigarette smoking.99 The sensitivity of CEA for the detection of pancreatic cancer has been described between 48 100 and 55%;101 the specificity between 87 100 and 90%.101 Due to the relatively low sensitivity and specificity, the role of the tumour markers CA 19-9 and CEA remains fairly limited in the context of diagnosing pancreatic cancer. However, the tumour markers are effective in clinical monitoring post-surgery or during chemotherapy, particularly in diagnosing recurrence.10

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Hi Clifford Yeah, thanks for that. I've read it yesterday or two days ago, I think. This is still some years away unfortunately but nevertheless it is very encouraging. Cheers.

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For those who are concerned how their condition may reflect on their kindred members; Importance of Age of Onset in Pancreatic Cancer Kindreds http://jnci.oxfordjournals.org/content/102/2/119.full Abstract Background Young-onset cancer is a hallmark of many familial cancer syndromes, yet the implications of young-onset disease in predicting risk of pancreatic cancer among familial pancreatic cancer (FPC) kindred members remain unclear. Methods To understand the relationship between age at onset of pancreatic cancer and risk of pancreatic cancer in kindred members, we compared the observed incidence of pancreatic cancer in 9040 individuals from 1718 kindreds enrolled in the National Familial Pancreas Tumor Registry with that observed in the general US population (Surveillance, Epidemiology, and End Results). Standardized incidence ratios (SIRs) were calculated for data stratified by familial vs sporadic cancer kindred membership, number of affected relatives, youngest age of onset among relatives, and smoking status. Competing risk survival analyses were performed to examine the risk of pancreatic cancer and risk of death from other causes according to youngest age of onset of pancreatic cancer in the family and the number of affected relatives. Results Risk of pancreatic cancer was elevated in both FPC kindred members (SIR = 6.79, 95% confidence interval [CI] = 4.54 to 9.75, P < .001) and sporadic pancreatic cancer (SPC) kindred members (SIR = 2.41, 95% CI = 1.04 to 4.74, P = .04) compared with the general population. The presence of a young-onset patient (<50 years) in the family did not alter the risk for SPC kindred members (SIR = 2.74, 95% CI = 0.05 to 15.30, P = .59) compared with those without a young-onset case in the kindred (SIR = 2.36, 95% CI = 0.95 to 4.88, P = .06). However, risk was higher among members of FPC kindreds with a young-onset case in the kindred (SIR = 9.31, 95% CI = 3.42 to 20.28, P < .001) than those without a young-onset case in the kindred (SIR = 6.34, 95% CI = 4.02 to 9.51, P < .001). Competing risk survival analyses indicated that the lifetime risk of pancreatic cancer in FPC kindreds increased with decreasing age of onset in the kindred (hazard ratio = 1.55, 95% CI = 1.19 to 2.03 per year). However, youngest age of onset for pancreatic cancer in the kindred did not affect the risk among SPC kindred members. Conclusions Individuals with a family history of pancreatic cancer are at a statistically significantly increased risk of developing pancreatic cancer. Having a member of the family with a young-onset pancreatic cancer confers an added risk in FPC kindreds. And; Alison Klein et al recently developed a computer-based pancreatic cancer risk prediction model called PancPRO.58 Using this tool, investigators and clinicians can enter an individual’s family cancer history and calculate their risk of developing pancreatic cancer. This tool is now available on the Web through CaGene (http://www.utsouthwestern.edu/utsw/cda/dept47834/files/68155.html).

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Forces For Cancer Spread Genomic Instability And Evolutionary Selection, Pancreatic Cancer Genomes Show Remarkable Mutation Effects Retweet Main Category: Pancreatic Cancer Also Included In: Genetics Article Date: 28 Oct 2010 - 2:00 PDT http://www.medicalnewstoday.com/articles/205978.php In new research published today, researchers uncover evolution in action in cancer cells. They show the forces of evolution in pancreatic tumours mean that not only is cancer genetically different between different patients, but each new focus of cancer spread within a patient has acquired distinct mutations. Effectively, ten different foci of cancer spread are ten different, but related, tumours. The complexity of pancreatic cancer genetics uncovered in this work helps to explain the difficulty of treating the disease but also strengthens the need for improved methods for early diagnosis. Pancreatic cancer is an aggressive malignancy with only two or three patients in one hundred living beyond five years from first diagnosis. The spread metastasis of the tumour is thought to be relatively symptomless in most patients until the disease is advanced. "We have always known that pancreatic cancer is a particularly aggressive disease," says Dr Peter Campbell, from the Wellcome Trust Sanger Institute and first author on the paper. "This study illustrates why it is so challenging. Each metastasis is its own tumour, each evolving, each striving for dominance, each adapting to life outside the pancreas. When we treat cancer that has spread through the body, we're not just treating one tumour, we might be treating tens of genetically distinct tumours." The researchers, from the Wellcome Trust Sanger Institute, near Cambridge, UK and the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins Medical Institutions, Baltimore, USA, looked at cancers in 13 patients who died from pancreatic cancer. They mapped rearrangements in the genomes of cancer samples: in some cases, they looked at several metastases from a patient. They discovered that pancreatic cancer genomes often contain a distinctive pattern of genome rearrangement that possibly reflects changes to repair mechanisms in the cancer cells. The pattern of mutation events is dramatically different to that found in breast cancer, for example. "With each study, cancer genomes are being revealed in their intricate complex detail," says Dr Andy Futreal, Head of Cancer Genetics and Genomics at the Wellcome Trust Sanger Institute and a senior author on the paper. "Genome instability is common in cancer, but this study has further revealed the dynamic nature of that instability and its role in spread of disease in the patient with instability being an engine of selection that allows the tumour to adapt to new sites in the body. "We can see a root of common lesions about half of the mutations are shared across metastases. Metastatic cancer is therefore like a family: the different deposits of tumour are genetically related to one another, as brothers, sisters and cousins are, but also have distinguishing genetic features that make them individual. Identifying and targeting the shared mutations with drugs is likely to be a route to more effective treatment." In a companion study Dr Iacobuzio-Donahue and her colleagues show that single-letter mutations show a similarly complex pattern. The team on that paper suggest that there might be a long time lag from the first cancer-causing mutations in the primary tumour to the violent and rapid metastasis of late-stage disease. Both papers suggest that the galloping mutation rate that develops produces cells that, because of specific mutations they acquire, can colonize other organs. Different combinations of active genes are needed to survive in different tissues. This is a return to the 120-year-old seed and soil hypothesis that some organs provide particularly fertile ground for particular cancer cells to grow. This work shows that even in one person's cancer, clones of cells can evolve genomes specialised for life in defined organs. The researchers emphasize that the shared mutations common to many early-stage pancreatic cancers could provide a route to discovery of new drug targets. In addition, the long time between the initial genetic changes in the developing primary cancer and spread to other organs might offer a window in which early diagnosis could detect disease while it is still curable by surgery. The patients for these studies were recruited to a programme established by Dr Iacobuzio-Donahue in Baltimore to develop new understanding of this difficult tumour type. Patients with terminal pancreatic cancer discuss with the team the aims of the research and choose whether or not to provide samples after their death. "We are so grateful to all patients who have discussed this programme," explains Dr Iacobuzio-Donahue from the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins Medical Institutions, Baltimore, Maryland and a senior author on the paper. "In times of tremendous personal difficulty, they and their families and friends have taken steps to help others, with the hope we can improve diagnosis and treatments in the future. The sacrifices they have made are now fundamentally improving our understanding of how pancreatic cancer develops and spreads. "This is a research paper, but we are all of us aware that there are real people behind these samples." Sources: Sanger Centre, AlphaGalileo Foundation.

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I find the below article easy to read and understand. You will find in the article everything you wanted to know about Pancreatic cancer and most common medical procedures including; - Aetiology - Pathology - Clinical features (markers, staging, imaging etc.) - Curative treatment - Palliation There are graphs that explain the Whipple's procedure and the whole process. Highly recommended. Pancreatic cancer Sarah C Thomasset Dileep N Lobo http://www.megaupload.com/?d=HVRVWVCX

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New Research From Infogroup's ORC Uncovers Numerous Factors Contributing To High Pancreatic Cancer Mortality Rate Article Date: 11 Jan 2011 - 5:00 PST http://www.infogroupcafe.com/wp-content/uploads/2010/12/Oncology_Pancreatic_Cancer_Review1.pdf

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University Of Oklahoma Scientists Discover Way To Stop Pancreatic Cancer In Early Stages Retweet Main Category: Pancreatic Cancer Also Included In: Cancer / Oncology Article Date: 13 Jan 2011 - 0:00 PST Cancer researchers at the Peggy and Charles Stephenson Oklahoma Cancer Center have found a way to stop early stage pancreatic cancer in research models - a result that has far-reaching implications in chemoprevention for high-risk patients. The research already has sparked a clinical trial in California, and the FDA-approved drug, Gefitinib, should be in clinical trials at OU's cancer center and others nationwide in about a year. The research appears in the latest issue of Cancer Prevention Research, a journal of the American Association for Cancer Research. C.V. Rao, Ph.D., and his team of researchers were able to show for the first time that a drug used in current chemotherapy for later stages of pancreatic cancer had a dramatic effect if used earlier. With low doses of Gefitinib, which has no known side effects at this level, scientists were able to not only stop pancreatic cancer tumors from growing, but after 41 weeks of treatment, the cancer was gone. "This is one of the most important studies in pancreatic cancer prevention," Rao said. "Pancreatic cancer is a poorly understood cancer and the focus has been on treatment in the end stages. But, we found if you start early, there will be a much greater benefit. Our goal is to block the spread of the cancer. That is our best chance at beating this disease." The Oklahoma cancer center research team said the finding points to an effective way to stop pancreatic cancer before it reaches later stages of development where the survival rate drops below 6 percent. Currently, most pancreatic cancer is not identified until the later stages. However, research is moving closer to the development of an early detection test for pancreatic cancer. When that is in place, Oklahoma cancer center researchers believe they now have a method to target the cancer before it spreads. Rao said OU officials and researchers will meet with other centers, including M.D. Anderson, whose specialists called the research "provocative," to discuss a pilot study in early 2011. Researchers hope to begin a Phase II clinical trial at the centers within 18 months. A Phase I trial is not required since the drug already has approval for human use from the U.S. Food and Drug Administration. The clinical trials will focus on at-risk patients, particularly those with an inflammation of the pancreas called pancreatitis. The drug also could help other high risk populations, including patients with a family history of pancreatic cancer and American Indian populations or others with Type 2 diabetes. Gefitinib works by targeting signals of a gene that is among the first to mutate when pancreatic cancer is present. By targeting the signal for tumor growth expressed by the mutated gene, researchers were able to stop the cancer's procession. "This gene is the key in 95 percent of cases of pancreatic cancer. It is our best target," Rao said. "By targeting this gene, we can activate or inactivate several other genes and processes down the line." Rao said the drug also could be effective in lung and colorectal cancer, but it is not known if it would work as well as in pancreatic cancer. The OU College of Pharmacy is assisting in the development of drugs and imaging techniques needed to further test Gefitinib with patients. Rao's research was funded by a grant from the National Cancer Institute. Located at the OU Health Sciences Center in Oklahoma City, the Peggy and Charles Stephenson Oklahoma Cancer Center is Oklahoma's only comprehensive academic cancer center, with significant programs in prevention, research, treatment and education. The center is working toward a National Cancer Institute "designated cancer center" status, the gold-standard of cancer research and treatment. More than 100 Ph.D.-level scientists are conducting innovative research at the center, and patients from every county in Oklahoma are treated by one of the largest oncology physicians groups in the state. Source: Diane Clay University of Oklahoma