More than a decade has passed since a groundbreaking article, The Hallmarks of Cancer, was published in Cell by Douglas Hanahan and Robert A.Weinberg that in many ways crystallized the scientific community’s “roadmap” for studying and treating cancer.  Now, the authors have revisited this framework in a recent article published in Cell, The Hallmarks of Cancer: the Next Generation, adding additional areas of focus underlying the tumor-host relationship, which promises to fuel additional work in the fight against cancer.

Much has happened since the original publication, in which the authors proposed six hallmarks of cancer development as a framework for how the complex multi-step process towards disease fits together. Unsurprisingly, research and treatment has focused during these years on targeted therapies, which specifically take aim at the “hallmark mechanisms” described by Hanahan and Weinberg.

The original six hallmarks of cancer development and examples of how treatments have been developed with these targets in mind include the following:

1. Sustaining proliferative signaling: Therapies include EGFR inhibitors
   
2. Evading growth suppressors: Therapies in development include cyclin-dependent kinase inhibitors
   
3. Activating invasion and metastasis: Therapies in development include inhibitors of HGF/c-Met
   
4. Enabling replicative immortality: Therapies in development include telomerase inhibitors
   
5. Inducing angiogenesis: Therapies include inhibitors of VEGF signaling
   
6. Resisting cell death: Therapies in development include proapototic BH3 mimetics

When in March of this year the authors published an update to their framework of cancer biology in Cell, they introduced four additional hallmarks of cancer development:

1. Avoiding immune destruction
2. Tumor-promoting inflammation
3. Genome instability and mutation
4. Deregulating cellular energetics

Already, the therapeutic implications of these additional hallmarks of cancer development are being targeted by researchers.

Therapies in development targeting cancer cells’ ability to avoid immune destruction include the area of immune activating anti-CTLA4 mAb agents. Many selective anti-inflammatory drugs are available and being developed to target tumor-promoting inflammation.  PARP inhibitors target genome instability and associated mutations. Finally, aerobic glycolysis inhibitors target deregulating cellular energetics.

The “road” from theoretical thinking to practical medical strategy to a well-funded study to an actual cancer therapeutic is travelled by many visionary researchers across the globe, one lab building on the finding of the other. Collectively, they inch towards the goal in the fight against cancer.

The significant value of Hanahan and Weinberg’s work is not in the development of safe, effective therapies themselves, but in the structure they provide to a highly competitive community of research scientists at countless institutions. Adding structure to this complex area of clinical research, without which, the scientific community would be less focused on the high impact anti-cancer targets, paves the way for thousands of studies in the areas that matter most, based on the underlying science.

It is the structure in thinking, and focus provided that is the key to progress. And with great optimism, we see a new, more comprehensive “roadmap” directing the world towards the next generation of anti-cancer therapies.