Recent developments in diagnosis of pancreatic cancer

Major advances in cancer control will be greatly aided by early detection for diagnosing and treating cancer in its preinvasive state before metastasis. Unfortunately, for pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death in the United States, effective early detection and screening are currently not available and tumors are typically diagnosed at a late stage, frequently after metastasis. Partly because of low sensitivity/specificity, existing biomarkers such as CA19-9 are not adequate as early detection markers of pancreatic cancer. Thus, a great need exists for new biomarkers for pancreatic cancer. This article focuses on recent developments in the identification of new serum protein biomarkers that are useful in the early detection of PDAC.

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Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden

F1000Research ◽

10.12688/f1000research.24654.1 ◽

2020 ◽

Vol 9 ◽

pp. 732 ◽

Cited By ~ 1

Author(s):

Annie He Ren ◽

Ioannis Prassas ◽

Antoninus Soosaipillai ◽

Stephanie Jarvi ◽

Steven Gallinger ◽

...

Keyword(s):

Pancreatic Cancer ◽

Serum Protein ◽

Biomarker Discovery ◽

Tumor Burden ◽

Antibody Microarray ◽

Cancer Heterogeneity ◽

Post Surgery ◽

Single Target ◽

Recent Developments ◽

Concentration Changes

Background: To account for cancer heterogeneity, we previously introduced the concept of “personalized” tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.

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Pancreatic cancer research: challenges, opportunities, and recent developments

Current Opinion in Gastroenterology ◽

10.1097/00001574-200209000-00007 ◽

2002 ◽

Vol 18 (5) ◽

pp. 563-567 ◽

Cited By ~ 3

Author(s):

Martin E. Fernandez-Zapico ◽

Joanna A. Kaczynski ◽

Raul Urrutia

Keyword(s):

Pancreatic Cancer ◽

Cancer Research ◽

Research Challenges ◽

Recent Developments

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Multi-Omic profiling (MoP) for patients (pts) with pancreatic cancer (PDA): Initial results of the Know Your Tumor (KYT) initiative.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.282 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 282-282 ◽

Cited By ~ 3

Author(s):

Michael J. Pishvaian ◽

Jonathan Robert Brody ◽

Lynn Matrisian ◽

Andrew Eugene Hendifar ◽

Anitra Engebretson ◽

...

Keyword(s):

Pancreatic Cancer ◽

Multiple Testing ◽

High Response Rate ◽

Survival Outcomes ◽

Cancer Type ◽

Molecular Abnormalities ◽

Pathway Activation ◽

Recent Developments ◽

Third Line ◽

Actionable Findings

282 Background: Emerging insights into the molecular biology of tumors and recent developments in MoP have led to the identification of targets that can be used for selecting treatment (tx) regimens. Multiple testing platforms are available, though most studies to date have used only next generation DNA sequencing (NGS). Methods: The Pancreatic Cancer Action Network (PanCAN) and Perthera have initiated an IRB-approved registry trial wherein we facilitate commercial MoP on tumor tissue from PDA patients. MoP includes NGS, immunohistochemistry (IHC), and phosphoproteomics (PHO). The results are reviewed by a team of PDA specialists in the context of the pt’s tx history. Tx options are prioritized based on the actionable molecular abnormalities. Pts are being followed longitudinally to assess physician acceptance of the tx options and track survival outcomes. Results: From 06/2014 to 09/2015, Perthera reports were delivered for 117 pts. 44% of the analyses were for second-line tx and 43% for ≥ third-line. Tumor based NGS and IHC were available for 75% and 90% of pts, respectively, and research use only PHO data was available for 20 pts. Actionable findings, defined based on a high response rate in pts with an identified molecular abnormality (in any cancer type), or based on a mechanism/pathway-defined implication of response to tx were identified in 43% of pts, primarily based on NGS. Incorporation of IHC refined and expanded chemotherapy tx options in all pts. PHO revealed pathway activation (e.g. mTOR, JAK-STAT, MET, RET, or EGFR) in 16/20 samples. Interestingly, only 45% of KRAS mutant samples had PHO-defined activation of the MEK-ERK pathway. Conclusions: MoP resulted in actionable findings in 43% of PDA pts using NGS and IHC. Incorporation of PHO data could have a significant impact on MoP-based therapy options. Analysis of the MoP in the context of patient history by a PDA specialist provided a service to treating oncologists in the community that was frequently incorporated into their treatment decisions. Survival outcomes will be presented. As additional testing platforms and results become available, the breadth and confidence of actionable markers is expected to increase.

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Precision Therapy of Pancreatic Cancer: From Bench to Bedside

Visceral Medicine ◽

10.1159/000509232 ◽

2020 ◽

Vol 36 (5) ◽

pp. 373-380

Author(s):

Katrin Jana Ciecielski ◽

Alexandra Berninger ◽

Hana Algül

Keyword(s):

Pancreatic Cancer ◽

Targeted Therapy ◽

Molecular Mechanisms ◽

Diagnostic Methods ◽

Ductal Adenocarcinoma ◽

Ongoing Research ◽

Precision Therapy ◽

Recent Developments ◽

Palliative Setting ◽

Insight Into

Background: Pancreatic ductal adenocarcinoma (PDAC), with a mortality rate of 94% and a 5-year-survival rate of only 8%, is one of the deadliest cancer entities worldwide, and early diagnostic methods as well as effective therapies are urgently needed. Summary: This review summarizes current clinical procedure and recent developments of oncological therapy in the palliative setting of metastatic PDAC. It further gives examples of successful, as well as failed, targeted therapy approaches and finally discusses promising ongoing research into the decade-old question of the “undruggability” of KRAS. Key Messages: Bench-driven concepts change the clinical landscape from “one size fits all” towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.

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Recent Developments and Current Issues in the Treatment of Pancreatic Cancer

Journal of Cancer Therapy ◽

10.4236/jct.2013.410a003 ◽

2013 ◽

Vol 04 (10) ◽

pp. 13-27 ◽

Cited By ~ 1

Author(s):

Helmut Oettle

Keyword(s):

Pancreatic Cancer ◽

Recent Developments

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Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden

F1000Research ◽

10.12688/f1000research.24654.2 ◽

2020 ◽

Vol 9 ◽

pp. 732

Author(s):

Annie He Ren ◽

Ioannis Prassas ◽

Antoninus Soosaipillai ◽

Stephanie Jarvi ◽

Steven Gallinger ◽

...

Keyword(s):

Pancreatic Cancer ◽

Serum Protein ◽

Biomarker Discovery ◽

Tumor Burden ◽

Antibody Microarray ◽

Cancer Heterogeneity ◽

Post Surgery ◽

Single Target ◽

Recent Developments ◽

Concentration Changes

Background: To account for cancer heterogeneity, we previously introduced the concept of “personalized” tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.

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Small Molecule KRAS Inhibitors: The Future for Targeted Pancreatic Cancer Therapy?

Cancers ◽

10.3390/cancers12051341 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1341 ◽

Cited By ~ 2

Author(s):

Josef Gillson ◽

Yogambha Ramaswamy ◽

Gurvinder Singh ◽

Alemayehu A. Gorfe ◽

Nick Pavlakis ◽

...

Keyword(s):

Drug Delivery ◽

Pancreatic Cancer ◽

Tumor Microenvironment ◽

Ductal Adenocarcinoma ◽

Antitumor Effects ◽

Nanoparticle Delivery ◽

The World ◽

Recent Developments ◽

Oncogene Homologue ◽

Pancreatic Cancer Therapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors in the world. Currently, there are no approved targeted therapies for PDAC. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are known to be a major driver of PDAC progression, but it was considered an undruggable target until recently. Moreover, PDAC also suffers from drug delivery issues due to the highly fibrotic tumor microenvironment. In this perspective, we provide an overview of recent developments in targeting mutant KRAS and strategies to overcome drug delivery issues (e.g., nanoparticle delivery). Overall, we propose that the antitumor effects from novel KRAS inhibitors along with strategies to overcome drug delivery issues could be a new therapeutic way forward in PDAC.

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Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates

Cancers ◽

10.3390/cancers13163946 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3946

Author(s):

Laura De Lellis ◽

Serena Veschi ◽

Nicola Tinari ◽

Zhirajr Mokini ◽

Simone Carradori ◽

...

Keyword(s):

Pancreatic Cancer ◽

Therapeutic Option ◽

Drug Repurposing ◽

Bioinformatic Analysis ◽

Mechanisms Of Action ◽

Immunomodulatory Agents ◽

Drug Candidates ◽

Unresectable Stage ◽

Recent Developments ◽

Toxic Drugs

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.

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