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Recent treatment advances and novel therapies in pancreas cancer: a review.

ABSTRACT:

Purpose

Over the last couple of years, we have witnessed the availability of a wide variety of different therapeutic agents and the identification of effective combinations of existing ones that have transformed the way we approach and treat pancreatic cancer. Proof of this are the recent validations that combinations of conventional chemotherapy drugs, the FOLFIRINOX regimen and gemcitabine plus nab-paclitaxel, significantly improves clinical outcomes in patients with metastatic disease. However, deeper and more sophisticated understanding of the biology of this cancer as well as the ability to develop better and perhaps more precise drugs predict that the landscape may be changing even more.

Methodology and results

In this review, we will summarize the most recent treatment advances including FOLFIRINOX, gemcitabine plus nab-paclitaxel and discuss novel approaches such as immune-mediated therapies, drugs that disrupt the tumor-stromal compartment, PARP inhibitors for BRCA pathway-deficient pancreatic cancer and new generations of conventional chemotherapeutics, which are in early phases of clinical development and have shown promising early results. We will also discuss some examples of drugs that failed, despite very good preliminary data, in order to appraise the lessons learned from these negative clinical trials. Lastly, we will comment on ongoing adjuvant and neoadjuvant trials.

Conclusion

We hope that at least some of these will result in positive trials and add to our armamentarium for treating this challenging malignancy.

SUBMITTER: Valsecchi ME

PROVIDER: S-EPMC4024386 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Progress in hemophilia therapy has been remarkable in the first 20 years of the third millennium, but the innovation began with the description the fractionation of plasma in 1946. The first concentrates followed the discovery of FVIII in the cryoprecipitate of frozen plasma and FIX in the supernatant in the early 1960s, which led to the initial attempts at replacement therapy. Unfortunately, the lack of screening methods for viral pathogens resulted in people with hemophilia (PWH) receiving concentrates contaminated by hepatitis A virus, hepatitis C virus, and human immunodeficiency virus, as these concentrates were made from large industrial pools of plasma derived from thousands of donors. Fortunately, by 1985, viral screening methods and proper virucidal techniques were developed that made concentrates safe. Increasingly pure products followed the introduction of chromatography steps with monoclonal antibodies in the production process. The problem of immunogenicity of exogenously administered concentrates has not yet had a complete solution. The development of alloantibodies against FVIII in about 25-35% of PWH is the most serious adverse effect of replacement therapy. The next major advance followed the cloning of the F8 gene and later the F9 genes, which paved the way to produce concentrates of factors obtained by the recombinant DNA technology. The injected FVIII and FIX molecules had a relatively short circulating half-life in the plasma of people with hemophilia A and B, approximately 12 and 18 hours, respectively. The ability to prolong the plasma half-life and extend the interval between injections followed the application of methods to conjugate the factor molecule with the fragment crystallizable of IgG1 or albumin or by adding polyethylene glycol, which has led to an increase in the half-life of concentrates, especially for rFIX. The next frontier in hemophilia therapy is the application of durable and potentially curative therapies such as with gene addition therapy. Experiments in hemophilia B have demonstrated durable responses. Unfortunately, the results with gene therapy for hemophilia A have not been as remarkable and the durability must still be demonstrated. Nonetheless, the long-term safety, predictability, durability, and efficacy of gene therapy for hemophilia A and B remain an open question. At present, only healthy adult PWH have been enrolled in gene therapy clinical trials. The application of gene therapy to children and those with pre-existing antibodies against the delivery vector must also be studied before this therapy becomes widespread.