Combinations of combinations of therapy to cure aggressive adult cancers
Summary of Strategic plan discussion #4
We believe curing aggressive adult cancers requires a different combination of therapy for each aspect of the malignant process, or “combinations of combinations” of therapy.
This essay is a nontechnical summary of our recently posted essay, Strategic plan to substantially reduce cancer deaths - discussion #4: curative therapy may require combinations of combinations of therapy.
Curative therapy for young adult cancers, such as leukemia or testicular cancer, typically targets cell growth and division, but still requires 4-5 different therapies for success.
This is because cell growth and division occur through a web of biological pathways; if one pathway is blocked, cell growth and division can occur through alternative pathways unless they are also blocked.
Cancer in adults is more difficult to cure than in children because its origin is more complex:
In children and young adults, cancer has a simple origin - in most cases, no cause is identified and there are no known risk factors, although it may be associated with inherited cancer predisposition or developmental mutations.
In contrast, adult cancer is often caused by risk factors acting over decades (tobacco use, excess weight, Western diet, alcohol, hormones and others) that cause premalignant and malignant changes to large areas of tissue (field effects); these field effects are uncommon in childhood cancer.
To cure aggressive adult cancer, we believe that multiple aspects of the malignant process must be targeted, not just cell growth and division. This includes systemic inflammation, immune system dysfunction, changes to neighboring tissue that support cancer growth (the tumor microenvironment), metastases and their microenvironment, hormones for some types of cancer and occasionally DNA variations present at birth.
Treatment of each aspect of the malignant process may require a different combination of therapies to be effective.
Thus, for a single patient, effective treatment may require combinations of combinations of therapies.
Of course, patients can only tolerate so much treatment at one time. Clinical trials, as described for childhood leukemia in Mukherjee: The Emperor of All Maladies: A Biography of Cancer for childhood leukemia, will be required to determine optimal combinations and delivery methods.