Cancer Gene Discovery: Past to Present

Cancer is a complex disease that originates from genetic changes leading to multiple phenotypic manifestations that ultimately result in suffering and death from cancer. Attempts have been made to define the phenotypic and genetic “hallmarks” of cancer, but many of these “hallmarks” remain descriptive, while the underlying mechanisms responsible for these hallmarks remain elusive. For decades, cancer researchers have been methodically identifying the molecular mechanisms that result in tumor initiation, growth, metastases, and resistance to therapy. Great strides forward have been made and we are entering an era of “precision medicine” with the goal of treating each cancer based on its unique etiology. Increasingly, the decision to use targeted therapies and immunotherapies in the clinic is based on the genotype of the cancer being treated. For example, specific tyrosine kinase inhibitors are only prescribed to patients that express the tyrosine kinase protein on their cancer cells. Likewise, a genetically unstable cancer is predictive for successful immunotherapy. Knowledge of the specific genetic changes that result in overproduction of oncogenes and reduced production of tumor suppressors is crucial for advancing therapeutic options for cancer. The first chapter of this book presents a brief history of cancer gene discovery. In the remaining chapters of this book, we present protocols using in silico, in vitro, and in vivo techniques for identifying genetic drivers of cancer, in the hope that these protocols will be used to increase our knowledge of the molecular mechanisms driving cancer.