Cancer Genomics Research: A Young and Exciting Field - NFCR


Cancer Genomics Research: A Young and Exciting Field

DNA strand

Genomics is an interdisciplinary field of science focusing on the structure, function, evolution, mapping and editing of genomes, which itself is a specific organism’s complete set of DNA, including all of its genes. While DNA was first isolated in 1869, and its structure identified in 1953, genomes were not first sequenced until 1970. Large-scale mapping of human genomes did not get underway until 1990, and was not completed until 2003. Myriad discoveries followed, from identifying a person’s genetic lineage to traits such as liking sour foods. For medical science, however, genomics holds the key to the genetic origins of cancer at the molecular level, which may be the biggest revolution in the history of medicine.

In genomics is the possibility of cancer treatments tailored to a specific individual. But even drugs whose origins are directly tied to genomics in one form or another and are widely-regarded as extremely effective, such as Gleevec and dasatinib, do not work in all cases (at least currently) and drug resistance has long been a reality. As the science of genomics progresses and technologies improve, targeted therapy that is both universally effective and immune to resistance could become a reality. To that end, several cancer initiatives associated with the U.S. National Cancer Institute (NCI) tap into genomics for their research:

  • The Clinical Trials Sequencing Project (CTSP), a collaboration among multiple NCI units, characterizes tissue samples from patients who have undergone standard-of-care or investigational treatments. These programs seek to understand the genomic basis of cancer development, metastasis and drug resistance.
  • Sometimes it is not drug resistance that is the mystery but, rather, the opposite. In some cases, a trial of a new drug fails to help most patients but one or two people treated with the drug benefit, sometimes spectacularly. The Exceptional Responders (ER) Initiative analyzes the genetic basis of exceptional responses to therapy.
  • ALCHEMIST, a set of precision medicine lung cancer trials, screens participants’ genomes for molecular targets of currently available targeted therapies. By analyzing patients’ tumors over the course of their treatment, the initiative aims to uncover how different cancers respond to targeted drugs and how tumors evolve during treatment.
  • The Cancer Genome Atlas contains the genetic information for cells of tumors taken from more than 11,000 patients, across 33 different types of cancer. Comparing this new data with normal samples allows for tremendously better analysis, diagnosis, treatment and prevention efforts.
  • The Human Models Cancer Initiative (HCMI) is generating new cancer models using cutting-edge technologies. These models will provide researchers with more accurate representations of a wide variety of cancers, and genomic characterization of the models may reveal links between genomic traits and how cells behave.

Beyond these endeavors, breakthroughs in cancer research thanks to genomics occur almost daily in labs across the globe. In August, Professor Yan Hai, a professor at Duke University, defined two novel molecular classifications of glioblastoma, completing the genetic map of TERTpWT-IDHWT (TERT promoter wildtype-IDH wildtype) glioblastoma. The groundbreaking findings might facilitate development of targeted therapies for fatal brain tumors.

Scientists in December 2018 found four transcription factors — HNF4A, HSF1, MECP2 and RAD21— were genomically demonstrated to be associated with the metastasis of colorectal cancer in both RNA and protein levels (transcription factors turn genes “on” or “off”).

As profound are these discoveries are, scientists are quick to add that development of any drug is anything but quick. Genomics can lay out a “map,” but the “vehicle” can take many years in the lab and clinical trials before coming to market. The process involves comparing and contrasting thousands of people’s genomes as well, which also takes time. That being said, thanks to genomics, 800 different anti-cancer drugs are in clinical development today.

Organizations such as the National Foundation for Cancer Research are key to these initiatives. Groundbreaking cancer genomics efforts by such NFCR fellows and affiliated scientists as Daniel Haber, M.D., Ph.D., Wei Zhang, Ph.D., and Brian Leyland-Jones, Ph.D., continue to bring promise.

Funding for such efforts is vital, as is financial support for those emerging sciences that do not have immediate application. Indeed, let us not forget that the field of cancer genomics is still in its adolescence!