Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer

Dipakkumar R. Prajapati; Caitlin Molczyk; Abhilasha Purohit; Sugandha Saxena; Reegan Sturgeon; Bhavana J. Dave; Sushil Kumar; Surinder K. Batra; Rakesh K. Singh

doi:10.1016/j.canlet.2023.216185

Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer

Dipakkumar R. Prajapati, Caitlin Molczyk, Abhilasha Purohit, Sugandha Saxena, Reegan Sturgeon, Bhavana J. Dave, Sushil Kumar, Surinder K. Batra, Rakesh K. Singh

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.

Original language	English (US)
Article number	216185
Journal	Cancer Letters
Volume	563
DOIs	https://doi.org/10.1016/j.canlet.2023.216185
State	Published - Jun 1 2023

Keywords

Angiogenesis
CXCR2 antagonist
Metastasis
Neutrophils
Pancreatic cancer
Tumor growth

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2023.216185

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title = "Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer",

abstract = "Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.",

keywords = "Angiogenesis, CXCR2 antagonist, Metastasis, Neutrophils, Pancreatic cancer, Tumor growth",

author = "Prajapati, {Dipakkumar R.} and Caitlin Molczyk and Abhilasha Purohit and Sugandha Saxena and Reegan Sturgeon and Dave, {Bhavana J.} and Sushil Kumar and Batra, {Surinder K.} and Singh, {Rakesh K.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = jun,

day = "1",

doi = "10.1016/j.canlet.2023.216185",

language = "English (US)",

volume = "563",

journal = "Cancer Letters",

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TY - JOUR

T1 - Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer

AU - Prajapati, Dipakkumar R.

AU - Molczyk, Caitlin

AU - Purohit, Abhilasha

AU - Saxena, Sugandha

AU - Sturgeon, Reegan

AU - Dave, Bhavana J.

AU - Kumar, Sushil

AU - Batra, Surinder K.

AU - Singh, Rakesh K.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.

AB - Pancreatic cancer (PC) has a poor prognosis, and current therapeutic strategies are ineffective in advanced diseases. We and others have shown the aberrant expression of CXCR2 and its ligands in PC development and progression. Our objective for this study was to evaluate the therapeutic utility of CXCR2/1 targeting using an small molecule antagonist, SCH-479833, in different PC preclinical murine models (syngeneic or xenogeneic). Our results demonstrate that CXCR2/1 antagonist had both antitumor and anti-metastatic effects in PC. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and recruitment of neutrophils, while it increased apoptosis. Treatment with the antagonist enhanced fibrosis, tumor necrosis, and extramedullary hematopoiesis. Together, these findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for inhibiting PC growth, angiogenesis, and metastasis.

KW - Angiogenesis

KW - CXCR2 antagonist

KW - Metastasis

KW - Neutrophils

KW - Pancreatic cancer

KW - Tumor growth

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DO - 10.1016/j.canlet.2023.216185

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AN - SCOPUS:85153180195

SN - 0304-3835

VL - 563

JO - Cancer Letters

JF - Cancer Letters

M1 - 216185

ER -

Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer

Abstract

Keywords

ASJC Scopus subject areas

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