Update on cancer therapeutics最新文献

The distribution of epigenetic alterations, such as DNA methylation and histone modifications, is abnormal in cancer cells, and drugs that influence these changes are currently being used effectively in the treatment of hematopoietic malignancies. Two hypomethylating agents, 5-azacytidine and decitabine, are FDA-approved for the treatment of myelodysplastic syndromes, and one histone deacetylase inhibitor, vorinostat, was recently FDA-approved for patients with refractory cutaneous T-cell lymphoma. Generally, these agents are very well tolerated, with myelosuppression being the major side effect. Although they are thought to work by re-organizing chromatin to allow expression of genes silenced by DNA hypermethylation and repressive histone modifications, the precise mechanism of action of these agents is not yet clear. Current studies are examining the utility of these agents for the treatment of solid tumors as well as testing these drugs in combination to treat a variety of malignancies.

Cancer in children has a low incidence. The type of malignancies differs substantially from tumors in adults. Since long-term event-free survival rates above 80% are noted in several tumors, it is estimated that in the future 1 in 750 adults will be a cancer survivor. Data on late effects are emerging and indicate that a large proportion of ex-patients has several and sometimes severe treatment sequelae. Minimizing treatment without loss of effectiveness in good risk cases and improving therapy in poor cases should be main goals in the future. In this review an update is given on tumor biology and treatment for several tumors, i.e. neuroblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, hepatoblastoma and germ cell tumors.

Although androgen deprivation therapy is widely accepted as the standard approach to patients with advanced prostate cancer, most patients eventually develop progressive disease despite castrate levels of testosterone. Despite its name, castration resistant prostate cancer (CRPC) is nonetheless dependent on continued activation of the androgen receptor via various signaling pathways. New secondary hormonal therapies seek to prolong suppression of the AR and thus delay the development of truly hormone “refractory” prostate cancer. Adrenal androgen synthesis represents one potential mechanism of continued AR-mediated growth in CRPC, and thus a potential target for therapy. Abiraterone acetate is an orally available small molecule that specifically inhibits the 17-alpha hydroxylase and C17,20-lyase enzymes within the adrenal steroid synthetic pathway. Preliminary data from phase I dose escalation trials suggest that PSA declines occur in a large proportion of patients and that the toxicity profile is acceptable. If ultimately proven to be efficacious in phase II/III trials, abiraterone acetate would represent the first agent mechanistically developed for the purpose of adrenal androgen suppression in prostate cancer.

Breast cancer is a significant public health burden with more than 200,000 new cases diagnosed in the United States each year. Although many incident cases represent localized disease, a significant proportion of women with early stage breast cancer eventually experience a distant relapse and ultimately die of metastatic breast cancer complications. Consequently, investigators strive to improve the adjuvant treatment paradigm and thus, optimize outcomes for women with early stage breast cancer. Within the last year a study describing a decline in incident breast cancer cases in the United States was reported. In addition, the results from a number of notable adjuvant treatment studies were reported or updated. Innovations in taxane-containing strategies and dose dense chemotherapy strategies were prominently featured. In addition, a number of insights pertaining to the treatment of women with HER2-positive breast cancer were reported. An overview of selected recently reported studies will be reviewed here.