Geneticists from Guangzhou China recently shocked

Geneticists from Guangzhou, China recently shocked the scientific community by publishing what appears to be the first attempt at using CRISPR–Cas9 genomic-editing technology to modify disease-associated DNAs from human embryos. The article appeared in the May 2015 issue of .
Despite the enormous progress in our understanding of cancer biology and significant investment in developing anticancer therapeutics, the mortality rates for many common cancers have not improved or have improved only slightly in the past two decades. Innovative approaches are needed to improve the efficacy and the therapeutic index of anticancer therapy. Nanomedicines based on nanometer-sized materials that carry therapeutic agents may hold the potential to improve tumor control and reduce treatment side effects by improving the pharmacokinetics and tumor deposition of the drug payloads (). In animal models, monotherapy nanomedicines successfully take advantage of prolonged blood circulation times to efficiently deliver therapeutic agents to tumors via the enhanced permeability and retention (EPR) effect. Nanomedicines have been modified with active targeting ligand and/or endowed with controlled release properties to further enhance tumor selectivity and drug deposition in cancer cyclooxygenase inhibitors which in turn enhances efficacy and reduces toxicity (). Clinically, however, nanomedicine formulations have largely failed to meaningfully improve the efficacy of chemotherapeutic interventions, in spite of their reduced toxicity. The two FDA-approved liposomal doxorubicin formulations Doxil® (PEGylated liposomal doxorubicin) and Myocet® (non-PEGylated liposomal doxorubicin) reduce most side effects (i.e. cardiomyopathy, bone marrow depression, alopecia and nausea) while increasing a few (palmar-plantar erythrodysesthesia and dermatologic toxicity). However, the formulations do not enhance anti-tumor effects in metastatic breast cancer, multiple myeloma, or Kaposi\'s sarcoma. Myocet® reduced the incidence of cardiac events and congestive heart failure, but showed no improvements in response rate or progression-free survival when compared to free doxorubicin in a Phase III trial in metastatic breast cancer patients. CRLX101, a polymeric micelle carrying camptothecin, was highly efficacious in animal studies but did not provide overall survival benefit when compared to best supportive care in a Phase 2b trial enrolling previously treated non-small cell lung cancer (NSCLC) patients (). There are several other examples of monotherapy nanomedicines that fail to produce enhanced response rates over conventional chemotherapy in clinical trials despite promising preclinical efficacy results in animal models. The reasons for the discrepancy between preclinical animal results and clinical human trial data are debated in the nanomedicine community, but we believe that the primary reasons are the less pronounced EPR effect in and the heterogeneity of human tumors as well as the intrinsic or acquired resistance to monotherapy. The less pronounced EPR effect in human tumors calls for nanomedicines with even superior pharmacokinetics and tumor deposition which are being actively pursued by researchers. Combination therapy can theoretically have an increased chance of addressing the issues of tumor heterogeneity and drug resistance. Cancers involve multiple pathways and often develop different successive mutations and intrinsic or acquired resistance as they progress (). In conventional mono-chemotherapy, spermatogenesis was long established that patients became less sensitive over the treatment courses as their cancers acquired resistance to the drug. Administration of multiple chemotherapeutics in a combination therapy has become a standard practice in conventional chemotherapy in order to take advantage of distinct mechanisms of action to overcome cross-resistance and achieve synergistically enhanced therapeutic outcome without significantly increasing toxicities. It is thus no surprise that recent clinical trials of nanomedicines have focused on evaluating the therapeutic efficacy of combination therapies.