Percentage Change in Plasma Cytokeratin 18 Is Associated with Clinical Outcomes in Patients Receiving Pemetrexed and Carboplatin for the Adenocarcinoma Subtype of NSCLC.

BACKGROUND: The adenocarcinoma subtype of non-small cell lung cancer (adeno-NSCLC) is routinely treated with chemotherapy if patients do not have molecular aberrations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements. There are currently no validated biomarkers that can predict if patients will gain clinical benefit from chemotherapy, leading to a majority of patients receiving many cycles of unnecessary chemotherapy. We hypothesized that the percentage rise in plasma caspase-cleaved cytokeratin 18 (cCK18) and total cytokeratin 18 (tCK18) assessed before and after chemotherapy correlates with the radiological response to chemotherapy. METHODS: Plasma samples from 40 patients with stage IV adeno-NSCLC, treated with first-line chemotherapy with carboplatin (AUC5) plus pemetrexed (500 mg/m(2)), were collected prior to chemotherapy and 48 h after treatment. ELISA was used to quantify cCK18 and tCK18. RESULTS: The male-to-female ratio was 3:1, and the median age of patients was 63 years. Patients who had a clinical benefit (complete response, partial response or stable disease) at the first radiological assessment following chemotherapy had a significantly higher percentage change in plasma tCK18 levels compared to those who had no clinical benefit, i.e. progressive disease (69.5 ± 75.1 vs. 25.3 ± 30.9%, respectively; p = 0.042). The receiver operating characteristic area was 0.712 (p = 0.039). There was an increase in the percentage change in cCK18 in patients with clinical benefit compared to those without clinical benefit but this was not statistically significant (57.6 ± 112.8 vs. 24.38 ± 45.1%, respectively; p = 0.85). CONCLUSIONS: The percentage change in plasma tCK18 levels before and after the first cycle of pemetrexed and carboplatin chemotherapy is associated with clinical benefit. If validated in larger cohorts, this test can be used to identify patients unlikely to respond to treatment who can thus be offered alternative treatments or entry into clinical trials.

Update on phase I studies in advanced pancreatic adenocarcinoma. Hunting in darkness?

Over the last twenty years, there is a limited number of effective cytotoxic or biological agents that managed to get approval in advanced pancreatic ductal adenocarcinoma. Despite numerous trials, investments in translational research and generally in health care, the survival of pancreatic cancer patients has improved by a few only months. This disappointing reality necessitates a better understanding of the pathogenesis of this disease and the identification of targetable alterations which might lead to development of more effective drugs or better combinations. At the 2013 Annual Meeting of the American Society of Clinical Oncology, few novel agents and new therapeutic concepts, tested in phase I studies in advanced pancreatic ductal adenocarcinoma, were presented. The first notable phase I study referred to the combination of chemotherapy with local delivery of silencing RNA against the K-ras mutation G12D, in advanced pancreatic ductal adenocarcinoma, which was well tolerated and promising (Abstract #4037). The second one referred to a combination of gemcitabine with pegylated recombinant human hyaluronidase (PEGPH20), an inhibitor of hyaluronan which as a matrix glycosaminoglycan is believed to play role in the reduced drug delivery to cancer (Abstract #4010). The other notable abstract was related to an early phase study which tested the safety and toxicity of arctigenin, a traditional herbal agent found in Arctium lappa Linné, administered as an oral formulation (GMS-01) in pancreatic ductal adenocarcinoma patient resistant to standard chemotherapy (Abstract #2559). The aforementioned early phase studies open new therapeutic approaches which deserve further testing in advanced pancreatic cancer.

Pharmacogenomics in pancreatic adenocarcinoma: new data and their clinical implications.

Despite advances and investments in translation research, clinical trials and health service in general, there is no significant impact on the survival of most patients diagnosed with advanced pancreatic adenocarcinoma. It is broadly recognized though that there is a small minority of patients who really benefit from particular treatments for reason usually not well understood. Light to this fact is gradually shed by developments in the field of pharmacogenomics, which plays pivotal role in what we call individualized medicine. In that perspective, it is of most importance to present the significant developments in pharmacogenomics announced in the recent 2013 American Society of Clinical Oncology Annual Meeting. First, the predictive role of hENT1, which codes for a gemcitabine transporter into cells, was highlighted and might help us decide whether we benefit from gemcitabine or 5-fluorouracil in the adjuvant setting (Abstract #4006). Second, authors presented the negative predictive role of SPARC stroma and cytoplasmic expression in patients treated with adjuvant gemcitabine (within the CONCO-001 study) as they reported poor outcome of those having high expression, not seen in patients on observation (Abstract #4016). Finally, a study which might be a basis for future strategies and as great food for scientific thought suggested that selection of cytotoxic treatment based on gene expression profiling is feasible in clinical practice and may help improve treatment efficacy as well as predict for drug resistance (Abstract #4017). Of course, there is a long way to go before implementation of these genomic findings, with the exception of hENT1 which seems to be close for clinical use.

Clinical and laboratory biomarkers in the management of pancreatic adenocarcinoma.

Despite improvements in the health service and the available treatment means, the outcome of the majority of patients with advanced pancreatic adenocarcinoma, even in the Western world, is disappointing. This fact necessitates invention and development of clinical and laboratory biomarkers that help us detect early enough those patients who have the worst prognosis, and who may benefit or not from our treatments and individualize thus our management accordingly. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting scientific works on biomarkers in pancreatic cancer were presented. Two of them presented new clinical data such as the correlation of hand and foot skin reaction with the prognosis of patients treated with capecitabine based treatment (Abstract #4023), and the independent association of early presentation of venous thromboembolic events with poor survival (Abstract #4037). The other two significant abstracts focused on new potential predictive laboratory biomarkers, such as the association of the baseline levels of serum albumin to benefit from bevacizumab enriched treatment (Abstract #4039) and the likely correlation of high insulin growth factor 1 (IGF-1) tissue expression to better prognosis in patients treated with the IGF-1 receptor monoclonal antibody (mAb) MK-0646 (Abstract #4054).

Novel agents and new combination treatments on phase I studies on solid tumors and pancreatic cancer.

Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not restrained by the existing current treatments. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, the results of few phase I clinical studies on solid tumors and pancreatic cancer were presented. In particular, in the field of immunotherapy, a pilot phase I study tested for first time a carcinoembryonic antigen (CEA)-based vaccine (Abstract #2561) on patients with pancreatic adenocarcinoma and another one the optimal dose and efficacy of trabedersen, an inhibitor of tissue growth factor-beta 2 (TGF-ß2) aiming to enhance antitumor immune responses (Abstract #4034). Other phase I studies explored the pharmacokinetic and pharmacodynamic properties of an oral gemcitabine pro-drug (LY2334737; Abstract #2554), or of the combination of gemcitabine with sirolimus (Abstract #3096) or the combination of gemcitabine with an inhibitor of mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK) (MEK 1/2; Abstract #4034).

Clinical studies in the second line setting of advanced pancreatic cancer: are we making any progress?

Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-ß2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer.

The role of endobronchial ultrasound in lung cancer diagnosis and staging: a comprehensive review.

Endobronchial ultrasound (EBUS) technology is a relatively new bronchoscopic method of visualizing the tracheobronchial tree, the surrounding pulmonary parenchyma, and the mediastinal structures, with a particular role in lung cancer diagnosis, staging, and treatment. There are 2 types of probes used in EBUS: the peripheral or radial probe (RP) and the linear or convex probe (CP) EBUS, which have technical differences and distinct diagnostic abilities. Both are used for EBUS-guided biopsies and transbronchial needle aspirations (TBNA), which increases the diagnostic yield over conventional bronchoscopic techniques, thus providing advanced information on staging, diagnosis, and treatment. Complications of EBUS are rare, and they are usually related to the underlying biopsy procedure and the operator's experience. EBUS examination duration is usually short, and it can be performed as an outpatient procedure. Interestingly, EBUS combinations with other current and evolving techniques, eg, electromagnetic navigation, are feasible and have a role in therapeutic interventions and molecular diagnostics. In conclusion, EBUS is a safe and accurate technique that is comparable with current criterion standard procedures, eg, mediastinoscopy. More training is required for the vast majority of respiratory physicians, and precise diagnostic algorithms are needed so that more patients benefit from this development.

Azithromycin pulses for the treatment of epidermal growth factor receptor inhibitor-related papulopustular eruption: an effective and convenient alternative to tetracyclines.

BACKGROUND: Papulopustular eruption (PPE) is the most common cutaneous side effect of epidermal growth factor receptor inhibitors (EGFRIs). OBJECTIVE: To document the efficacy and safety of pulsed azithromycin doses in the treatment of EGFRI-related PPE. METHODS: A retrospective analysis of patients under EGFRIs who exhibited at least grade 2 PPE and were intolerant or resistant to tetracyclines was performed. Treatment consisted of pulsed azithromycin doses of 500 mg daily for 3 consecutive days per week for at least 2 weeks. RESULTS: Treatment with azithromycin showed a significant reduction in the number of lesions in 18/20 patients, with 11 showing complete resolution of the rash. No significant side effects were recorded. We did not observe any interactions with the targeted biological agents or any obvious compromise of the anticancer treatment. CONCLUSIONS: Weekly pulses of azithromycin are effective and promote increased patient adhesion to the treatment. A prospective study is needed to confirm efficacy and safety of this convenient treatment.

Novel agents in early phase clinical studies on refractory pancreatic cancer.

The standard current treatment options in advanced pancreatic cancer have demonstrated minimal or modest only efficacy for the majority of patients. Unfortunately, the mortality and morbidity remain high crying out for better treatments and results. With the exception of erlotinib, which received approval by the Food and Drug Administration of the United States in 2005, no other novel agents have since been added in our treatment quiver. Therefore, the search for novel approaches continuous at the laboratory and clinical level. At the 2012 American Society of Clinical Oncology Gastrointestinal Symposium, results of some interesting early phases clinical studies were presented. First, in Abstract #198, toxicity and efficacy results from the phase I/II study of cixutumumab, an insulin growth factor-1 receptor (IGF-1R) antibody combined with the standard gemcitabine and erlotinib treatment were presented, but the outcomes suggest no real clinical benefit. Second, the early safety and clinical data from the novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer patients were presented (Abstract #233) and again no particular efficacy was observed. Finally, interesting results which definitely deserve further exploration were presented in Abstract #211, which tested the combination of ipilimumab, an antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4), with a cell-based vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene in advanced refractory pancreatic cancer. Though, it seems we have not yet found the culprit and the solution of this devastating disease, a small step forward might have been achieved.

Translational research. New findings and potential future applications in pancreatic adenocarcinoma.

The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patients and clinicians alike. Still, in the dawn of 2012, most patients are diagnosed at a late stage where cure is not feasible, with the majority going to succumb within the same year of diagnosis. Thus, the only hope for early and diagnosis and radical treatment is the invention of diagnostic and prognostic tests which might predict accurately patients who may develop this disease and those who have the most aggressive potential, so clinician adopt the appropriate strategy. In this paper we summarize the findings from the three most interesting research abstract as presented at the 2012 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #160 which shows the diagnostic utility of microRNA serum profiling in pancreatic cancer patients, on Abstract #201 which suggests a potential prognostic role of transforming growth factor (TGF)-beta pathway in advanced pancreatic cancer, and on Abstract #165 which shows that protein S100A4 might be a new, potentially useful, predictive biomarker of gemcitabine efficacy.

The efficacy of gemcitabine as salvage treatment in patients with refractory advanced colorectal cancer (CRC): a single institution experience.

OBJECTIVE: To assess the efficacy of gemcitabine based chemotherapy in heavily pre-treated patients with advanced colorectal cancer. PATIENTS AND METHODS: Patients, who had been treated with gemcitabine 1250-2000 mg/m² biweekly in combination with capecitabine 1700-2000 mg/m²/day, d1-7 every two weeks were retrospectively reviewed. All the patients had previously received at least three chemotherapy regimens and 12 (55%) had also received a 4th line regimen. All the patients had been treated with a monoclonal antibody either against vascular endothelial growth factor receptor (VEGFR) or endothelial growth factor receptor (EGFR) (only if wild-type KRAS). The patients had had blood tests weekly, carcinoembryonic antigen (CEA) level measurement every 4 weeks and radiological assessment of their disease with CT scans every 8/9 weeks. RESULTS: Twenty two patients were included; male-female, 14:8; age ranged from 43-73 years. The majority of the patients (17/22) had performance status (PS) ECOG 0-1 and the remaining patients (5/22) had PS 2 at the time of initiation of the gemcitabine-based regimen. Thirteen patients demonstrated a clinical benefit (2 partial response, 2 minor response, 9 stable disease), 6 patients progressed and 2 were not evaluable. CONCLUSION: Gemcitabine has a modest activity in heavily pre-treated colorectal cancer patients and may be an option in good performance status patients.

Biomarkers and pharmacogenetics in pancreatic cancer. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.

Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs) that is associated with positive efficacy of gemcitabine (Abstract #4022); the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657); the re-affirmation of plasma cytidine deaminase (CDA) as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645); and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO) trial in an attempt for epidermal growth factor receptor (EGFR) pathway biomarker identifications (Abstract #4047).

Updates on first-line treatment of metastatic pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.

Despite the extensive research, mounting knowledge in the cancer field and enormous investments, pancreatic cancer remains a rather incurable disease with aggressive natural course and high mortality rate. The very slow progress is a result of the complex pathogenesis of this disease, which prevents us from targeting the culprit and making a step forward. Therefore, the field is still unexplored and this is a real challenge and opportunity for new ideas and novel approaches. In this paper, we will present the most interesting studies in the first line pancreatic cancer setting, presented at the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting. While there are few studies testing the role of combining the cytotoxic S-1 and gemcitabine, the majority of the studies are examining the safety and impact of adding to the classic gemcitabine treatment novel molecular agents which target key pathways or overexpressed proteins.

Pancreatic neuroendocrine tumors: role of novel agents. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

Neuroendocrine tumors of pancreas (PNET) are very rare, consisting of heterogeneous histological subtypes with a variable natural history and different clinical manifestations. Although the vast majority of these neoplasms are sporadic, it is possible to be part of a genetic syndrome such as multiple endocrine neoplasia 1 (MEN-1) or tuberous sclerosis (TSC). When systemic treatment is required the options are limited and management strategy is generally based on experts' consensus or clinical experience. The prognosis is usually better than in pancreatic adenocarcinoma, though poorly differentiated PNET behave aggressively and survival is shortened. Since last year, there has been a significant advance in the management of PNET, after reported data confirmed the efficacy of everolimus, an mTOR inhibitor, in patients with advanced disease. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium, updated results of the phase III trial (RADIANT-3) regarding the efficacy of everolimus in PNET (Abstract #158) were reported, along with the results of a subgroup analysis of the Japanese patients enrolled in this study (Abstract #289). Another agent with promising activity in PNET which will be discussed in this review is sunitinib, a biological agent with multikinase inhibitor properties (Abstract #244).

Translational research in pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

The high mortality rate of pancreatic cancer places this uncommon malignancy quite high as a cause of cancer related deaths. Compared to other solid tumors, there is a lag in the development of new effective drugs and the actual clinical benefit remains poor over the last decade or so. The lack of therapeutic options necessitates the invention of the important molecules playing role in pancreatic carcinogenesis and the development of specific targeted therapies. Treatment advances have to be proven first in the bench before applying them at the bedside, thus why translational research is so needed. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, preclinical evidence was presented regarding the efficacy of C4 compound against focal adhesion kinase (FAK) (Abstract #214), the role of the cyclooxygenase-2 (COX-2) inhibitor apricoxib in enhancing the efficacy of gemcitabine and erlotinib (Abstract #227) and the role of curcumin and ABT-888 (a poly-ADP ribose polymerase (PARP) inhibitor) as potent radiosensitizers (Abstracts #222 and #203). Interestingly, the invention of a novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer cell lines exhibited notable antibody-dependent cellular cytotoxicity (Abstract #235). Finally, enhanced selective targeting of pancreatic tumors was achieved by combining antibody-drug conjugates (ADC) with radioimmunotherapy (Abstract #206).

Translational research in pancreatic cancer. Highlights from the "2010 ASCO Gastrointestinal Cancers Symposium". Orlando, FL, USA. January 22-24, 2010.

Pancreatic cancer is an aggressive type of cancer ranking as the 10th most common cancer and the 4th cause of cancer related deaths. Due to disappointing treatment results and outcome of pancreatic cancer patients there is urgent need for better understanding of pathogenesis, mechanisms of tumor progression and resistance to treatment in order to achieve etiological approach. The development of the field of translational research and pharmacogenomics during the last several years has revealed many molecular pathways being aberrant in pancreatic cancer. This knowledge has led to the identification of biomarkers with prognostic or predictive value and the development of novel drugs against specific abnormal targets of pancreatic tumors. In this year's ASCO Gastrointestinal Cancers Symposium, researchers presented data showing evidence of biomarkers with prognostic value (Abstracts #166, #140, and #126) and genetic polymorphisms predicting possibly efficacy of gemcitabine treatment (Abstract #166). The development of the new small molecule CRT0066101 targeting the protein kinase D (PKD), which is upregulated significantly in pancreatic cancer cells was also presented (Abstract #159). This small molecule blocked specifically PKD and inhibited potently in vitro and in vivo the growth of pancreatic cancer cells. Furthermore, a retrospective analysis of KRAS status on resected pancreatic cancer specimens showed that frequency of KRAS mutations was 67% (57% of those were on codon 12), lower than previous reported in more advanced stages (Abstract #169). In this paper we present details and comment on these works.

The molecular targets for the diagnosis and treatment of pancreatic cancer.

Pancreatic cancer is considered an aggressive malignancy that responds poorly to current treatments and therefore has a dismal survival rate. This disease is usually not diagnosed until a late stage, at which point palliative chemotherapy with the purine analogue gemcitabine and/or a fluoropyrimidine or a platinum agent is the standard approach. There are some new data on the molecular and genetic changes that take place in pancreatic cancer, which may facilitate the accuracy of diagnosis and efficacy of treatments. However, translational efforts in clinical practice have increased clinicians' options with a targeted agent, erlotinib, in combination with the standard gemcitabine chemotherapy. Many other novel drugs currently being tested in the field of pharmaco-oncology target various altered biological pathways and molecules. Nevertheless, the lack of clinically significant improvements in treatments is rendering efforts to develop methods of early diagnosis both more urgent and promising. The aim of this review was to summarize the molecular basis of pancreatic carcinogenesis and the latest developments in diagnosis by molecular means, focusing on the results of clinical research into targeted and personalized treatments.

Pharmacogenetics in pancreatic cancer. Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.

Cancer pharmacogenetics is a popular and evolving field in medicine with applications in various types of tumours helping clinicians to apply a more personalized medicine by providing information of prognostic, predictive and therapeutic value. Such evidence of pharmacogenetic applications is been already available in colon cancer (e.g. KRAS status, mismatch repair genes status, UGT1A1 polymorphisms), lung cancer (EGFR mutations, ERCC1 mutations), breast cancer (HER2/neu overexpression) and many others. In all these tumors, the genetic information is rendering the management of the involved patients safer and more effective. Interesting abstracts and announcements from the perspective of pharmacogenomics in pancreatic cancer included Abstract #4611 which suggested the use of a novel genomic study able to detect specific single nucleotide polymorphisms (SNPs) with prognostic value, Abstract #4615 which showed that the known proteins alpha1-antitrypsin and alpha1-antichymotrypsin may be predictive of response to gemcitabine and survival, and Abstract #11097 which suggested that human R protein (HuR) expression may be a useful predictive biomarker of gemcitabine treatment. The authors also present here a few other abstracts of pharmacogenomic interest which had negative findings, but believed to be of clinical importance.

Pancreatic cancer: translating lessons from mouse models.

Pancreatic cancer is the 10th most common cancer and 4th cause of cancer related deaths. Progress in diagnosis and treatment has been slow and disappointing but improvement in understanding of pathogenesis and of molecular changes may offer some ground for rational and etiological approach. During the last ten years the first evidence about the benefit of targeting dysregulated pathways was provided by the study that tried the addition of the EGFR inhibitor erlotinib to the standard cytotoxic gemcitabine. Since then, despite other numerous negative studies, various agents have been investigated in the preclinical and clinical setting and are currently through drug development pipeline. In this year's Gastrointestinal Symposium of the American Society of Clinical Oncology (GI ASCO, San Francisco, 15-17 January 2009), translational and clinical researchers presented evidence of specific genetic variations predicting toxicity (Abstract #115) or efficacy (Abstract #118) of gemcitabine-based treatment and of clinical biomarkers which may serve as predictors of therapy (Abstract #117) or mortality (Abstract #202). We were also informed about the presence of a new surface antigen (CD133) in pancreatic cancer stem cells (Abstract #150) and the development of a recombinant viral vector carrying the G antigen 1 (GAGE1) gene able for B-cells transduction (Abstract #178), which may lead potentially to the development of new immunotherapies and targeted agents. Study and efficacy of novel targeted molecules in preclinical models in vitro and in vivo was also presented (Abstracts #144, 145, 158, 163). In contrast to other malignancies, no mutations of the EGFR/PI3K pathway were found in pancreatic cancer cells not allowing thus a patients' selection approach for EGFR antibodies (Abstract #173).

Therapeutic tools in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lower survival rate than other digestive tract tumors. It remains a therapeutic challenge with limited active agents. Honing our current understanding of markers of toxicity and response, and individualizing treatment with the prognostic and therapeutic tools available are important to make a worthy impact on a patient's course. The authors summarize selected abstracts from the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, USA, January 15-17, 2009. The Symposium featured pancreatic cancer in 84 research abstracts, of which, seven are reviewed that focus on markers of toxicity: cytidine deaminase (Abstract #151) and haptogloin (Abstract #167) as markers of gemcitabine toxicity; markers of response: use of PET scan for prognosis (Abstract #157), and correlations with CA 19-9 to post-chemo-radiation resectability (Abstract #215) and time to progression (Abstract #160); and individualized applications: characterizing the phenotypic similarities between a patient tumor and the direct xenograft (Abstract #154) and a report about the poor outcome of patients with ascites (Abstract #220). Validated clinical tools that can assist in managing patients through the narrow therapeutic window are needed.