From an Egyptian Papyrus to the Hallmarks of Cancer: A Journey through the Development of Knowledge in Oncology Research

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The word “cancer” was used for the first time in ancient Greece by Hippocrates, often termed the Father of Medicine for his contributions to modern medical practice. Even prior to its naming, descriptions of human cancer can be traced back to Egypt around 3000 BC in the Edwin Smith Papyrus. The author(s) wrote of tumors or ulcers of the breast, removed by cauterization, and for which “there is no treatment.”

It took many thousands of years until the first possible treatment for tumors was suggested. In the 1700s, Scottish surgeon John Hunter stated, “if the tumor was moveable…There is no impropriety in removing it.” At least in this way, some pre-metastatic lesions could be cured.

In the last half of the 20th century, a great amount of progress was achieved due to a drastic leap forward in technology and basic biological understanding. During an international symposium sponsored by the WHO in 1950, the medical community was stunned by the unexpected variation of types of cancers in different parts of the world, and by learning that people who migrated to other countries developed types of cancer common to those countries, rather than their homelands. This evidence indicated that most cancers were caused by environmental exposure, not by inherited genetic factors.

As scientists learned that chemicals, radiation, and viruses could cause cancer, they came to the realization that it was genetic alterations that lead to the development of cancer. A major difference between healthy and cancer tissue is that healthy cells with severely damaged DNA should die by apoptosis, or alternatively be destroyed by the immune system. Mutations in two key types of genes play a major role in the initiation of cancer and enable the damage we see in cancer genomes, those that activate oncogenes or inactivate tumor suppressors. Oncogenes are those genes that by activating mutation or other genomic alteration can promote tumor formation. By contrast, tumor suppressors are the genes that by inactivating mutation or genomic loss cannot properly prevent tumor formation, usually by removing regulation for cell division, apoptosis, and DNA damage repair. While tumor formation, or tumorigenesis, is now known to be much more complex than this, this initial simple understanding had fantastic power to move the field forward into the era of genomics.

In a seminal peer-reviewed paper published in Cell in 2000 and updated in 2011, Douglas Hanahan and Robert Weinberg provided a framework for rationalizing and understanding cancer’s biology summarized in 6 distinctive and complementary principles (hallmarks) governing the transition from a normal to a cancer cell. Their work provided the scientific community with a solid foundation for understanding the biology of cancer and a solid foundation for cancer research. Those seminal hallmarks are sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis.

Acquisition of the hallmarks is made possible by two “enabling characteristics”, the most prominent of which is the development of genome instability, which generates the genetic diversity by mutations and chromosomal rearrangements. The second characteristic is inflammation, driven by immune cells that can supply growth factors, pro-angiogenic factors, enzymes facilitating cell invasiveness, and inducing signals that lead to activation of hallmark-facilitating programs.

The authors also identified two emerging hallmarks: reprogramming energy metabolism and evading immune destruction. The latter has become a vitally important aim of cancer research, as we discover a myriad of ways in which cancer hijacks adaptive immune checkpoints and modulates the innate immune response to prevent destruction.

The Hallmarks of Cancer has become one of the most widely recognized roadmaps for understanding cancer. Its profoundly simple yet comprehensive framework defines a distinct set of acquired capabilities that distinguish cancer from healthy tissue. The holistic vision became the foundation of some of NanoString’s most established and utilized cancer-focused gene expression panels.

Nanostring has created a rich portfolio of panels devoted to oncology research. The panels are expertly curated, containing up to 800 genes and allowing for up to 55 customized additional unique targets. The true star of our oncology panels dedicated to the hallmarks of cancer is undoubtedly the Tumor Signaling 360 Panel (TS 360), a dynamic tool developed to profile the tumor, immune response, and microenvironment comprehensively.

The TS 360 Panel has three core themes. “Tumor signaling” measures the gene expression of molecular pathways covering 6 hallmarks focused on tumor-intrinsic factors – cellular energetics, sustained proliferation, evading growth suppressors, enabling replicative immortality, genomic instability & mutations, and resisting cell death. “Immune Response” focuses on the two hallmarks dedicated to tumor-immune interaction: immune evasion and tumor-promoting inflammation. Finally, “Microenvironment” covers invasion & metastasis as well as angiogenesis, the final hallmarks that detail the role of the other factors in the cellular milieu impacting cancer.

This comprehensive panel is optimized for the current state of oncology, where we grapple with the increasingly complex and interconnected world of tumor signaling. As therapeutics targeting the tumor evolve, we need a greater understanding of tumor signaling in the proper context of the tissue milieu and immune response. The NanoString TS 360, with its 40+ pathways covering all ten hallmarks and their underlying molecular mechanisms, represents exactly this approach.

The TS 360 panel is run on the nCounter® system. Researchers can take advantage of a platform that accurately and robustly measures gene expression in RNA extracted from FFPE samples – often highly degraded but ubiquitous in clinical practice – with less than 15 minutes hands-on time. The panel is available for human and mouse samples for all types of pre-clinical research.


  1. The Edwin Smith Surgical Papyrus. By James Henry Breasted. Vol.1
  2.  Higginson J, Muir CS, Munoz M. Introduction to epidemiology. In: Human Cancer: Epidemiology and Environmental Causes., editor. Cambridge, England: Cambridge University Press; 1992. pp. xvii–xxv, esp xx, xxii, xxiii
  3. Douglas Hanahan, Robert A Weinberg. Hallmarks of cancer: the next generation. Cell 2011 Mar 4;144(5):646-74.

For Research Use Only. Not for use in diagnostic procedures.

By Laura Tabellini Pierre
For research use only. Not for use in diagnostic procedures.