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Nanoparticles from Marine Biomaterials for Cancer Treatment
Published in Se-Kwon Kim, Marine Biochemistry, 2023
The U.S. Food and Drug Administration (FDA) has approved a number of important anticancer drugs derived from marine organisms, such as cytarabine (Cytosar U®), a chemotherapeutic drug used to treat leukemia. Trabectedin (Yondelis®) is another antitumor agent that is used to treat advanced soft tissue sarcoma. Breast, prostate, and pediatric sarcomas are all in clinical studies. Another anticancer medication, eribulin mesylate (Halaven®), is used to treat breast cancer and liposarcoma. Brentuximab vedotin (Adcetris®) is an antibody-drug conjugate (ADC) medication used to treat HL and anaplastic large cell lymphoma that has relapsed or become resistant. Midostaurin (Rydapt®) is a protein kinase inhibitor used to treat acute myeloid leukemia and myelodysplastic syndrome (van Andel et al. 2018). Furthermore, 19 anticancer substances obtained from the sea are at various stages of clinical testing (Zuo and Kwok 2021). Numerous studies have also demonstrated the anticancer properties of marine-derived chemicals in vitro or in vivo.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The EMA and FDA have granted Orphan Drug Status to trabectedin for the treatment of soft-tissue sarcomas and ovarian cancer. It is also being studied in clinical trials for use in breast and prostate cancer, and pediatric sarcomas. In the UK, trabectidin is used for the treatment of advanced soft-tissue sarcoma (STS) when treatment with anthracyclines and ifosfamide has failed or is contraindicated, and for relapsed platinum-sensitive ovarian cancer (in combination with pegylated liposomal doxorubicin). STS is one of the most difficult forms of cancer to treat. The majority of chemotherapeutic agents have only marginal activity against STS, with the most active agents (e.g., doxorubicin and ifosfamide) providing objective response rates of approximately 20% as first-line treatments, and with their use limited by serious toxicities and resistance. It is administered by intravenous infusion, and a corticosteroid such as dexamethasone is given by intravenous infusion 30 minutes before therapy for its antiemetic and hepatoprotective effects.
Sarcomas
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Chemotherapy has only limited activity. Doxorubicin remains the chemotherapy of choice for most sarcomas but in some subtypes or with certain molecular changes other agents may be indicated, e.g. ifosfamide in synovial sarcoma, paclitaxel in angiosarcoma and eribulin in liposarcoma. Trabectedin has been shown to have activity and other newer agents are showing promise in clinical trials.
Real-world evidence of the efficacy and tolerability of trabectedin in patients with advanced soft-tissue sarcoma
Published in Expert Review of Anticancer Therapy, 2020
Luis Miguel de Sande González, Javier Martin-Broto, Bernd Kasper, Jean-Yves Blay, Axel Le Cesne
A retrospective study was conducted with data from the French compassionate-use program which evaluated long-term outcomes in 181 patients with advanced STS from 11 centers between 2003 and 2008 [12]. Trabectedin was administered according to the approved regimen of 1.5 mg/m2 in 24-h continuous infusion every 21 days. Patients received a median of 3 cycles (range: 1–19). Over a median follow-up period of 64 months, PFS and OS in the whole population were 3.6 and 16.1 months, respectively. Considering efficacy by treatment line for trabectedin, median OS decreased from 33.4 months on first-line (when doxorubicin and ifosfamide were administered in the peri-operative setting) to 18.2 months on second-line, 14.3 months on third-line, and 10.2 months on fourth-line chemotherapy. Trabectedin was also evaluated in patients who continued treatment after six cycles (n = 56 patients in stable disease or partial response). Of these, 40 patients continued treatment for a median of 9 cycles. Patients who received ≥7 cycles of trabectedin showed significantly longer PFS (10.5 months) and OS (33.4 months) than those patients who discontinued treatment after 6 cycles (5.3 and 13.9 months; p = 0.001 and p = 0.009, respectively). These results have been corroborated by the subsequent phase II randomized T-DIS trial mentioned above.
The place of trabectedin in the treatment of soft tissue sarcoma: an umbrella review of the level one evidence
Published in Expert Opinion on Orphan Drugs, 2019
Pavlina Andreeva-Gateva, Shenol Chakar
Compared to other drugs used to treat STS, trabectedin has a very favorable safety profile. Two of the most commonly used drugs in STS – doxorubicin, and ifosfamide, show cumulative toxicity to the heart and kidneys, respectively. Patients who respond to trabectedin treatment may experience long periods of disease control and may tolerate treatment for months due to the lack of cumulative toxicity [24], demonstrating the safety and good tolerance of the drug. In addition to lack of organ toxicity, it does not cause many of the side effects that aggravate the quality of life in patients undergoing anti-tumor treatment, such as severe nausea, mucositis, alopecia or cutaneous toxicity. While such adverse effects may be tolerated for a short time, they become more severe in prolonged treatment, and their absence from the spectrum of adverse effects is essential. Commonly reported adverse effects of trabectedin anemia, neutropenia, nausea/vomiting, and elevations in aspartate aminotransferase and alanine aminotransferase [30].
Insights into apoptotic proteins in chemotherapy: quantification techniques and informing therapy choice
Published in Expert Review of Proteomics, 2018
Trabectedin, an antitumor compound, is clinically effective in soft-tissue sarcoma. Ewing’s sarcomas are characterized by the expression of an aberrant transcription factor, the EWS-FLI1 fusion protein, known to regulate more than 500 genes required for the oncogenic transformation and survival of Ewing’s tumor cells [69]. Trabectidin activates apoptosis through the inhibition of EWS-FLI1 [70]. Even after prolonged responses to drug treatment, frequently resistance develops in sarcoma. The comparison of mRNAs, miRNAs and proteins profiles of 402–91 and 402–91/ET cells identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402–91 and 402–91/ET cell lines. Transcriptomic and proteomic data revealed apoptosis and cell cycle regulation that could play a key role in modulating trabectedin resistance. The results have to be validated in in vivo models and liposarcoma patients with different sensitivity to trabectedin treatment [71].