open access
Reflections on 2015
Bruce A. Chabner
Author Affiliations
Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA-
We close a year of remarkable progress in cancer research and care, and make special note of some important trends that this journal is embracing. On the research front, I first would like to recognize two notable achievements that have changed expectations for the future. The first is clustered regularly interspaced short palindromic repeats (CRISPR) technology, which will allow excision of mutant or defective genes and insertion of a physiological alternative. Put simply, we now have the power to remake human DNA. As an example of its potential, this technology could correct inherited disorders that predispose to cancer, or could insert new genes that resist infection by carcinogenic viruses such as HIV, hepatitis B or C, human papillomavirus, or Epstein-Barr virus. Many other applications to cancer are possible. Second, we have witnessed the vast expansion of immunotherapy with checkpoint inhibitors, and the introduction to trial of a series of complementary immunotherapies (vaccines, other checkpoint inhibitors, T-cell and macrophage activators). In the coming year, we expect to learn much more about how to use these expensive drugs more efficiently, developing biomarkers that predict response, and limiting their use to patients who will benefit.At the same time, we have learned a great deal about targeted therapy and its limitations. Increasingly, we are seeing that tumors are not simple BRAF or ALK mutants but a collection of subclones that emerge down diverse pathways. Treating the drug-resistant tumor will not be a simple task. We have harvested valuable information from sequential biopsy specimens of primary tumor and have learned that drug resistance is polyclonal, complex, and daunting. Plasma DNA may prove a better picture of the diversity of mutations throughout the body than a biopsy specimen from a single site. Other uses of plasma DNA monitoring are appealing. For example, plasma sampling after local treatment may be able to predict who among adjuvant-treatment candidates is likely to recur after local therapy. We will be featuring molecular tumor board papers that aid the reader in interpreting results of these and other molecular assays, and in choosing new treatments based on these findings. Despite the enormity of the problem of resistance, the contribution of targeted therapy has been profound, providing treatment options for otherwise incurable tumors.What about the early trials that fail or lead to equivocal results? These results deserve to see the light of day. I would like to note that our Clinical Trial Results (CTR) section, chaired by Susan Bates and Tito Fojo, continues to provide a much-needed path to publication of early clinical trial results. The failure to publish many valuable trials has awakened the attention of Congress and the National Cancer Institute. There is no reason not to publish these trials, given the support available online from CTR.....
