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Chagas disease research and development: Is there light at the end of the tunnel?

ABSTRACT: Chagas disease, or American trypanosomiasis, is the result of infection by the parasite Trypanosoma cruzi. It is endemic in Latin America, and spreading around the globe due to human migration. Although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. Indeed, the current status of evidence and data available does not allow any absolute statement related to treatment needs and outcome for Chagas patients to be made. Although there has been some new impetus in Research and Development for Chagas disease following recent new clinical trials, there is a scientific requirement to review and challenge the current status of evidence and define basic and clinical research priorities and next steps in the field. This should ensure that the best drugs for Chagas disease are developed, but will require a focused and collaborative effort of the entire Chagas disease research community.

SUBMITTER: Chatelain E

PROVIDER: S-EPMC5196238 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Chagas disease research and development: Is there light at the end of the tunnel?

Chatelain Eric E

Computational and structural biotechnology journal 20161214

Chagas disease, or American trypanosomiasis, is the result of infection by the parasite <i>Trypanosoma cruzi</i>. It is endemic in Latin America, and spreading around the globe due to human migration. Although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. Indeed, the ...[more]

PMID: 28066534

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Project description:Due to extremely poor prognosis, pancreatic cancer (PDAC) represents the fourth leading cause of cancer-related death in Western countries. For more than a decade, gemcitabine (Gem) has been the mainstay of first-line PDAC treatment. Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results. Recently, the field of systemic therapy of advanced PDAC is finally moving forward. Polychemotherapy has shown promise over single-agent Gem: regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control, although sometimes at the cost of poor tolerability. The PRODIGE 4/ACCORD 11 was the first phase III trial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX; however the less favorable safety profile and the characteristics of the enrolled population, restrict the use of FOLFIRINOX to young and fit PDAC patients. The nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells. Regardless of whether or not this is its main mechanisms of action, the combination of nab-Paclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints. Furthermore, recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC, particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control. Here, we provide an overview of recent advances in the systemic treatment of advanced PDAC, mostly focusing on recent findings that have set new standards in metastatic disease. Potential avenues for further development in the metastatic setting and current efforts to integrate new effective chemotherapy regimens in earlier stages of disease (neoadjuvant, adjuvant, and multimodal approaches in both resectable and unresectable patients) are also briefly discussed.

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Chagas disease research and development: Is there light at the end of the tunnel?

Publications

Chagas disease research and development: Is there light at the end of the tunnel?

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