SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas

Pascual‐Pasto, Guillem; Castillo‐Ecija, Helena; Unceta, Nora; Aschero, Rosario; Resa-Pares, Claudia; Gómez‐Caballero, Alberto; Vilà-Ubach, Mònica; Muñoz‐Aznar, Oscar; Suñol, Mariona; Burgueño, Victor; Gómez-González, Soledad; Sosnik, Alejandro; Ibarra, Manuel; Schaiquevich, Paula; Álava, Enrique de; Tirado, Óscar M.; Mora, Jaume; Carcaboso, Ángel M.

doi:10.1016/j.jconrel.2021.12.035

Cited by 22 publications

(11 citation statements)

References 36 publications

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“…The high efficiency and low toxicity of nab-Paclitaxel might take advantage of enhanced concentration of free taxon, active transportation through endothelial cells, and penetration into tumor tissue by albumin binding to secreted protein acidic and rich in cysteine receptor. A recent study has shown that SPARC plays an important role in tumor uptake of nab-paclitaxel ( 28 ). Furthermore, a phase 3 trial showed that nab-paclitaxel may enhance the anticancer activity of atezolizumab, a PD-L1 antibody, in untreated metastatic triple-negative breast cancer ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

et al. 2022

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BackgroundCancer of unknown primary (CUP) is heterogeneous and has a wide variety of clinical presentations and a poor prognosis in most patients, with a median overall survival of only 6 months. The development of molecular profiling contributes to precision therapy, and targeted drugs and immune checkpoint inhibitors (ICIs) greatly promote individualized treatment.Case presentationHere, we reported a case of an unfavorable subset of CUP who had a long time of survival after the immunotherapy-prominent comprehensive treatment. A 48-year-old man presented with back pain and a cough. A diagnostic work-up showed bone marrow, multiple bones, and lymph node metastasis. Lymph node pathology implies metastatic poorly differentiated cancer. Next-generation sequencing (NGS) showed no special targets, but the tumor proportion score (TPS) of programmed death-ligand 1 (PD-L1) was 80% and the tumor mutation burden (TMB) was 16.7 per million bases. After two cycles of pembrolizumab 200 mg D1 plus nanoparticle albumin-bound (nab)-paclitaxel 200 mg D1&8 (q3w), PET-CT and bone marrow aspiration cytology showed a complete response (CR). Subsequently, pembrolizumab alone was used for three months. The left inguinal lymph nodes showed new metastasis. After two cycles of the combination treatment of pembrolizumab and (nab)-paclitaxel, a partial response (PR) was achieved. After seven months, retroperitoneal lymph nodes showed new metastasis, and the sequential treatment with radiotherapy and pembrolizumab exhibited encouraging efficacy. To date, the patient has survived nearly 40 months with the combination therapy.ConclusionsThe ICI-prominent comprehensive treatment provided clinical benefit for the reported case of CUP. Thus, CUP patients with markers of benefiting from immunotherapy should be actively treated with immunotherapy to improve their prognosis.

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Section: Discussionmentioning

confidence: 99%

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

et al. 2022

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“…EWS PDX with high expression of SPARC was associated to accumulation of nab-paclitaxel showing better drug responses compared to tumors with lower SPARC levels. Consistently, pediatric tumors that express SPARC were able to accumulate nab-paclitaxel for more extended periods of time [ 163 ]. Nab-paclitaxel is being evaluated in several clinical trials including an active phase II clinical trial in monotherapy for patients with EWS and other tumors (NCT03275818).…”

Section: Nanotherapy: a Refined Target-specific Drug Delivery Systemmentioning

confidence: 90%

“…A recent work evaluated the albumin-bound (nab)-paclitaxel NPS in PDXs of EWS, rhabdomyosarcoma, and osteosarcoma [ 163 ]. These NPS bind to tumor cells that express SPARC, a secreted acidic protein and rich in cysteine that shows a high affinity to bind albumin.…”

Section: Nanotherapy: a Refined Target-specific Drug Delivery Systemmentioning

confidence: 99%

“…These NPS bind to tumor cells that express SPARC, a secreted acidic protein and rich in cysteine that shows a high affinity to bind albumin. Nab-paclitaxel was less bound in SPARC-knocked down (SPARC-KD) compared to SPARC-WT cells [ 163 ]. EWS PDX with high expression of SPARC was associated to accumulation of nab-paclitaxel showing better drug responses compared to tumors with lower SPARC levels.…”

Section: Nanotherapy: a Refined Target-specific Drug Delivery Systemmentioning

confidence: 99%

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Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies

Sánchez-Molina

Figuerola-Bou

Sánchez-Margalet

et al. 2022

Cancers

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Ewing Sarcoma (EWS) is an aggressive bone and soft tissue tumor that mainly affects children, adolescents, and young adults. The standard therapy, including chemotherapy, surgery, and radiotherapy, has substantially improved the survival of EWS patients with localized disease. Unfortunately, this multimodal treatment remains elusive in clinics for those patients with recurrent or metastatic disease who have an unfavorable prognosis. Consistently, there is an urgent need to find new strategies for patients that fail to respond to standard therapies. In this regard, in the last decade, treatments targeting epigenetic dependencies in tumor cells and the immune system have emerged into the clinical scenario. Additionally, recent advances in nanomedicine provide novel delivery drug systems, which may address challenges such as side effects and toxicity. Therefore, therapeutic strategies stemming from epigenetics, immunology, and nanomedicine yield promising alternatives for treating these patients. In this review, we highlight the most relevant EWS preclinical and clinical studies in epigenetics, immunotherapy, and nanotherapy conducted in the last five years.

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“…Mechanistically, because it is less toxic and more penetrating, a higher tumor/plasma paclitaxel drug ratio in favor of nab-paclitaxel was observed ( 119 ). Because secreted protein acidic and rich in cysteine (SPARC) shows high binding affinity to albumin, a study has proved that pediatric sarcoma xenografts expressing SPARC would show enhanced uptake and accumulation of nab- paclitaxel ( 120 ). We therefore infer that nab-paclitaxel is likely to be more effective in sarcomas.…”

Section: Efficacy Of Traditional Taxanes and Nab-paclitaxel In Sarcomasmentioning

confidence: 99%

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas

Tian

Yao

2022

Front. Oncol.

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Taxanes (paclitaxel and docetaxel) play an important role in the treatment of advanced sarcomas. Albumin-bound paclitaxel (nab-paclitaxel) is a new kind of taxane and has many advantages compared with paclitaxel and docetaxel. Nab-paclitaxel is currently approved for the treatment of advanced breast, non-small cell lung, and pancreatic cancers. However, the efficacy of nab-paclitaxel in sarcomas has not been reviewed. In this review, we first compare the similarities and differences among nab-paclitaxel, paclitaxel, and docetaxel and then summarize the efficacy of nab-paclitaxel against various non-sarcoma malignancies based on clinical trials with reported results. The efficacy and clinical research progress on nab-paclitaxel in sarcomas are also summarized. This review will serve as a good reference for the application of nab-paclitaxel in clinical sarcoma treatment studies and the design of clinical trials.

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SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas

Cited by 22 publications

References 36 publications

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies

Albumin-Bound Paclitaxel: Worthy of Further Study in Sarcomas

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