Advances in Chemotherapy for Pancreatic Cancer

Sirohi, Bhawna; Singh, Ashish; Dawood, Shaheenah; Shrikhande, Shailesh V.

doi:10.1007/s13193-014-0371-y

Cited by 5 publications

(3 citation statements)

References 89 publications

(103 reference statements)

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“…1 Many approaches are currently available to treat cancer, and chemotherapy still remains the dominant one due to its high efficiency. [2][3][4] Over the past few decades, a number of therapeutic drugs have been discovered and translated into the clinic, such as paclitaxel, doxorubicin, and cisplatin. Traditional administration of these drugs, however, has suffered from several serious drawbacks that limit their clinical use, including poor solubility, non-specic tissue sequestration, unwanted sideeffects, and drug resistance by tumors.…”

Section: Introductionmentioning

confidence: 99%

Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy

Yang

Mao

et al. 2019

RSC Adv.

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Tumor targeting delivery of chemotherapeutic drugs by nanocarriers has been demonstrated to be a promising strategy for cancer therapy with improved therapeutic efficacy. In this work, we reported a novel type of active targeting micelle with pH-responsive drug release by using biodegradable poly(lactide)-poly(2-ethyl-2-oxazoline) di-block copolymers functionalized with spermine (SPM). SPM has been considered as a tumor binding ligand through its specific interaction with the polyamine transport system (PTS), a transmembrane protein overexpressed on various types of cancer cell, while its application in nano-drug delivery systems has rarely been explored. The micelles with spherical shape ($110 nm) could load hydrophobic paclitaxel (PTX) with high capacity, and release the payload much faster at acidic pH (4.5-6.5) than at pH 7.4. This pH-responsive property assisted the rapid escape of drug from the endo/lysosome after internalization as demonstrated by confocal laser scanning microscopy images using coumarin-6 (Cou-6) as a fluorescent probe. With surface SPM modification, the micelles displayed much higher cellular uptake than SPM lacking micelles in various types of cancer cells, demonstrating tumor targeting ability. The uptake mechanism of SPM modified micelles was explored by flow cytometry, which suggested an energy-consuming sag vesicle-mediated endocytosis pathway. As expected, the micelles displayed significantly enhanced anti-cancer activity. This work demonstrates that SPM modified pH-sensitive micelles may be potential drug delivery vehicles for targeting and effective cancer therapy.Scheme 1 Tumor targeting delivery of SPM functionalized micelles via PTS binding and their endocytosis and pH-triggered endo/lysosome drug release for anti-cancer therapy.This journal is

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Section: Introductionmentioning

confidence: 99%

Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy

Yang

Mao

et al. 2019

RSC Adv.

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“…However, in majority of pancreatic cancer cases, the post-surgery relapse of the disease leads to a highly aggressive and metastatic form that does not respond to any therapy. Patients suffering from advanced stage local tumor have a slightly longer median survival of 6–10 months, but those reported with metastatic stage of the disease have a mere 3–6 months of median survival rate (4–8). Chemotherapy remains the only option for treatment of metastatic pancreatic cancer even though the approach tends to be mostly palliative with no major survival advantage (4).…”

Section: Introductionmentioning

confidence: 99%

EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model

Singh

Mattheolabakis

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time and with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution.

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“…Systemic therapy is required for pancreatic cancer in all stages, and surgery is the only approach to significantly improve survival and outcomes . Neoadjuvant therapy (NAT) may be recommended for patients with locally advanced pancreatic cancer (LAPC) , and FOLFIRINOX regimens are first‐line neoadjuvant chemotherapies for LAPC worldwide . However, the promotion of NAT for Chinese patients with LAPC has been a challenge.…”

mentioning

confidence: 99%

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population

Guo

et al. 2018

The Oncologist

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Lessons Learned. Modification of FOLFIRINOX significantly improves safety and tolerability in Chinese patients with locally advanced pancreatic cancer. Patients with locally advanced pancreatic cancer benefit from neoadjuvant therapy and experience a much better survival than patients with upfront surgery. Background. The objective of this study was to evaluate the efficacy of modified‐FOLFIRINOX (mFOLFIRINOX) regimens in Chinese patients with locally advanced pancreatic cancer (LAPC) and to compare outcomes between patients with LAPC treated with mFOLFIRINOX‐based neoadjuvant therapy (LAPC‐N) and patients with LAPC who underwent upfront surgery (LAPC‐S). Methods. Forty‐one patients with LAPC‐N were enrolled prospectively. Imaging features, chemotherapy response, adverse events, perioperative complications, histology, and survival were analyzed. Seventy‐four patients with resectable pancreatic cancer (RPC) (from April 2012 to November 2017) and 19 patients with LAPC‐S (from April 2012 to March 2014) were set as observational cohorts, and data were collected retrospectively. LAPC‐N patients with adequate response underwent surgical treatment, whereas continuous chemotherapy was given to LAPC‐N patients who were not deemed resectable after treatment, and the response was re‐evaluated every 2 months. Results. Forty‐one patients with LAPC received mFOLFIRINOX with a response rate of 37.1%. The most common severe adverse events were neutropenia and anemia. mFOLFIRINOX‐based neoadjuvant therapy contributed to a remarkable decrease in CA19‐9 level and tumor diameter. Fourteen LAPC‐N patients underwent surgery (LAPC‐N‐S) after downstaging. Compared with LAPC‐N‐S cases, LAPC‐S patients had longer operative time, more blood loss, and a higher risk of grade 5 complications. The median overall survival (OS) and progression‐free survival (PFS) of LAPC‐N‐S patients were 27.7 months and 19.3 months, respectively, which were similar to those of patients with RPC (30.0 months and 23.0 months) and much longer than those of patients with LAPC‐S (8.9 months and 7.6 months), respectively. Conclusion. Neoadjuvant chemotherapy such as the mFOLFIRINOX regimen can be recommended for Chinese patients with LAPC after dose modification. Patients with LAPC‐N who underwent surgery obtained significantly improved survival compared with patients in the observational LAPC‐S cohort, who did not undergo neoadjuvant therapy.

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Advances in Chemotherapy for Pancreatic Cancer

Cited by 5 publications

References 89 publications

Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy

Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy

EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population

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