Precision Medicine for Gastrointestinal Cancers: a Conference Report

Şahin, Ibrahim Halil

doi:10.2144/fsoa-2020-0061

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…[17,18] These disappointing ndings have resulted in signi cant loss of interest in SHH inhibitors and most recently, other stroma modifying agents including PEGPH20, a pegylated version of hyaluronidase, was investigated in metastatic PDAC patients. The combination of this agent with FOLFIRINOX and gemcitabine nab-paclitaxel chemotherapies did not result in any survival bene t and led to detrimental outcomes in patients who received PEGPH20 with concurrent FOLFIRINOX, [19][20][21].…”

Section: Background and Materialsmentioning

confidence: 97%

Pancreatic Cancer Stem Cells May Define Tumor Stromacharacteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

Askan

Şahin

Chou

et al. 2020

Preprint

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Background Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Methods PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate density, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P = 0.089). Conclusions These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.

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Section: Background and Materialsmentioning

confidence: 97%

Pancreatic Cancer Stem Cells May Define Tumor Stromacharacteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

Askan

Şahin

Chou

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…These disappointing ndings have resulted in signi cant loss of interest in SHH inhibitors and most recently, other stroma modifying agents including PEGPH20, a pegylated version of hyaluronidase, was investigated in metastatic PDAC patients. The combination of this agent with FOLFIRINOX and gemcitabine nab-paclitaxel chemotherapies did not result in any survival bene t and led to detrimental outcomes in patients who received PEGPH20 with concurrent FOLFIRINOX, [18][19][20].…”

Section: Introductionmentioning

confidence: 97%

Pancreatic Cancer Stem Cells May Define Tumor Stroma Characteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

Askan

Şahin

Chou

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.Methods: PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results: N= 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p=0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P=0.089). Conclusions: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.

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“…These novel drug development concepts have led to a dramatic shift in the paradigm of cancer treatment in solid tumors. For example, comprehensive molecular profiling with the next generation of sequencing has evolved significantly and is currently standard of care in advanced stage solid tumors including pancreatic adenocarcinoma [ 3 , 4 ] . Upfront analysis of molecular alterations that are in actionable genes provides a framework to guide the therapy for personalized medicine.…”

Section: Introductionmentioning

confidence: 99%

The tumor microenvironment of pancreatic adenocarcinoma and immune checkpoint inhibitor resistance: a perplex relationship

Şahin¹,

Türen²,

Santapuram³

et al. 2020

CDR

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Pancreatic cancer is one of the most aggressive cancers with a high mortality rate even among patients with earlystage disease. Although recent studies with novel therapeutic approaches have led to modest improvement in survival outcomes, limited progress is achieved for the use of immunotherapeutics in this challenging cancer. Immune checkpoint inhibitors, thus far, single-agent or in combination, have not yielded significant improvement in survival outcomes except in mismatch repair-deficient pancreatic cancer. The tumor microenvironment of pancreatic cancer has been considered as an attractive target for over a decade based on preclinical studies that suggested it may adversely affect drug delivery and antitumor immunity. In this review article, we elaborate on the biology of pancreatic cancer microenvironment, its highly complicated interaction with cancer cells, and the immune system. We also discuss plausible explanations that led to the failure of immune checkpoint inhibitors as therapeutic agents and the potential impacts of pancreatic cancer stroma on these negative studies.

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Precision Medicine for Gastrointestinal Cancers: a Conference Report

Cited by 4 publications

References 25 publications

Pancreatic Cancer Stem Cells May Define Tumor Stromacharacteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

Pancreatic Cancer Stem Cells May Define Tumor Stromacharacteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

Pancreatic Cancer Stem Cells May Define Tumor Stroma Characteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

The tumor microenvironment of pancreatic adenocarcinoma and immune checkpoint inhibitor resistance: a perplex relationship

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