SPARC is a possible predictive marker for albumin-bound paclitaxel in non-small-cell lung cancer

Abstract

ObjectivesNanoparticle albumin-bound paclitaxel (nab-paclitaxel) produced good tumor response in cases with lung squamous cell carcinoma, one of the most difficult cancers to treat. Secreted protein acidic and rich in cysteine (SPARC) binds to albumin, suggesting that SPARC plays an important role in tumor uptake of nab-paclitaxel. There is as yet no predictive marker for cytotoxic agents against non-small-cell lung cancer (NSCLC), and hence we believed that SPARC expression might be associated with tumor response to nab-paclitaxel.Patients and methodsWe studied stromal SPARC reactivity and its association with clinicopathological characteristics in 200 cases of NSCLC using a custom tissue microarray fabricated in our laboratory by immunohistochemical staining. We also investigated the relationship between stromal SPARC reactivity and tumor response to nab-paclitaxel using biopsy or surgical specimens obtained from advanced or recurrent lung cancer patients.ResultsHigh SPARC stromal reactivity (>50% of optical fields examined) was detected in 16.5% of cases and intermediate SPARC reactivity (10%–50%) in 56% of cases. High expression in cancer cells was rare (five cases). Stromal SPARC level was correlated with smoking index, squamous cell carcinoma, and vessel invasion. Furthermore, patients with high stromal SPARC reactivity in biopsy specimens such as transbronchial lung biopsy or surgical specimens tended to respond better to nab-paclitaxel.ConclusionStromal SPARC was detected by immunohistochemical staining in ∼70% of NSCLC cases, and good tumor response to nab-paclitaxel was correlated with high stromal SPARC reactivity. SPARC may be a useful predictive marker for selecting patients likely to respond favorably to nab-paclitaxel treatment.

The role of weekly nanoparticle albumin bound paclitaxel monotherapy as second line or later treatment for advanced NSCLC in China

“…Whether SPARC expression was a predictive biomarker to Nab-PTX therapy remains controversial. Some literatures [ 36 , 37 ] found that high stromal SPARC expression in the primary tumor might be a biomarker for Nab-PTX treatment of inferior PFS and OS in advanced pancreatic ductal adenocarcinoma and better survival in NSCLC. However, another study reported that SPARC expression did not seem to be associated with the efficacy of Nab-PTX in metastatic breast cancer [ 38 ].…”

Efficacy and Safety of Nab-Paclitaxel as Second-line Chemotherapy for Locally Advanced and Metastatic Non-small Cell Lung Cancer

“…Nab-paclitaxel is a new paclitaxel and its tolerability, bioavailability and efficacy have been improved compared to standard paclitaxel (10). Nanoparticles of albuminpaclitaxel are absorbed by tumor cells from which paclitaxel is subsequently released to kill tumor cells (11). Compared with standard paclitaxel, nab-paclitaxel has an average particle size of 130 nm with minimal risk of capillary blockage (12) and enhances delivery of the cytotoxic agent to cancer cells.…”

Second-line afatinib administration in an elderly patient with squamous cell carcinoma

“…In this case, the patient had a remarkable response with only 28 days of administration. Of note, in a recent study, the overexpression of secreted protein acidic and rich in cysteine (SPARC), which binds to albumin, was used as marker of treatment efficiency with afatinib 22. The patient did not have any adverse effects from the afatinib 40 mg administration.…”