President Obama has called for a “cancer moonshot” in order to make America “the country that cures cancer once and for all.” An infusion of money and talent of the magnitude contemplated by such a program into cancer research would be huge boon to the cancer research community that has witnessed a continuing decline in funding over the last 15 years. Despite this erosion in funding, two exciting new advances in the treatment of cancer have evolved that have the potential to greatly improve the survival rate for cancer patients while at the same improving the quality of life for cancer survivors. These two significant areas of research and investigation are targeted therapies and immunotherapy. Both developments have the potential to grow and evolve the most in the next ten years and offer new market opportunities while more importantly, offer the greatest hope for the effective treatment for cancer patients coupled with an increase in survival rates.
The starting point for discussion is the Human Genome Project (the HGP) which was completed in 2003. The goal of the HGP was to identify and map all of the human genome from both a physical and functional standpoint.
The success of the HGP in turn contributed to the start of The Cancer Genome Atlas (the TCGA) in 2003. The goal of the TCGA was to map out the genetic mutations of solid cancer tumors using genome sequencing and bioinformatics. The TCGA, along with the earlier unique discoveries of HER2 and EGFR in breast and lung cancer tumors respectively, dramatically changed the way researchers viewed the treatment of cancer.
Historically, researchers believed that all tumors were alike based on their site of origin; e.g. all non-small cell lung cancer (NSCLC) tumors were alike and therefore one treatment would work in all instances. The failure of standard chemotherapy and radiation treatments for many cancer patients with same cancers did not support the thesis. Gaining the ability to analyze tumors at the molecular level, researchers learned that just like snowflakes, no two tumors are alike. It is now understood that each tumor has its own unique genetic mutations. Many of the genetic mutations have the ability to be targeted with a specific drug that will reduce or even kill the tumor. This variously termed precision medicine, personalized medicine or targeted therapy.
The development of targeted therapies has also created new markets coupled with the development of disciplines related to the delivery of targeted therapies to include: biopsies, testing, identification of genetic mutations and treatments. By way of example, a single biopsy at initial diagnosis used to be considered the standard of care. Today, it may be necessary to conduct multiple biopsies throughout the course of a patient’s treatment as a single biopsy may not detect or identify all of a tumor’s mutations. Moreover, we have come to learn that while a targeted therapy often works for a period of time, because a tumor has multiple mutations, as one mutation shrinks other less populated mutations, may in turn grow. In response, researchers are looking to combine treatments that target different mutations.
Aside from the toxicity and tolerability of these cocktails, it remains a challenge to identify these mutations. While it is acknowledged that there are many mutations, there is no agreement though as to whether to test for the one, two or three mutations that have current Federal Drug Administration (FDA) approved treatments or use Next Generation Sequencing (NGS) that can identify all mutations, understanding that most are not targetable at this time. Research continues with an expanding focus on developing therapies for more and more mutations. Most academic centers, as a standard practice, will perform some level of NGS whereas community centers, where over 80% of cancer patients are treated, do not have the facilities or resources to perform NGS. Developing an accessible, timely and affordable NGS could be a major step forward in the world of cancer treatment.
Another issue is tissue and its availability for use in both the targeted therapy and immunotherapy setting. Tumor tissue is a valuable yet limited resource. Attaining additional tissue may not only be difficult but it may also place the patient at additional risk for other medical complications. In response, there has been a rapidly emerging area of research in liquid biopsies. The belief is that tumors shed their cells which can then be found in blood, urine, saliva, mucus, etc. Identifying these so-called circulating tumor cells (CTC’s) in bodily fluids could dramatically improve early cancer diagnosis when most cancers are easiest to treat. Most clinicians and researchers do not think liquid biopsies are sensitive enough or reliable enough yet for clinical applications. It seems only a matter of time though before liquid biopsies may become the standard of care. Potential cost savings involved in the identification, diagnosis and treatment determination through liquid biopsies rather than tissue biopsies would be a definite “moonshot”. Some liquid biopsies are being used today to help determine if a patient will respond to specific treatments.
In the 1890’s, William Coley began the first experiments on cancer immunotherapy by injecting toxic bacteria into a person’s tumor. The question he was trying to answer was how to get a person’s own immune system to recognize a cancerous cell as foreign and therefore allow the immune system’s t-cells to attack and kill the cancer. Immunotherapy has been the subject of cancer research ever since but it has only been within the last 5 years that tangible, consistent results began to be realized. Cancers with a greater mutational burden such as melanoma and lung cancer seem to respond well to antibodies that disrupt the immune checkpoint PD1 binding to PDL1. But it is still unclear why some patients respond well and others do not. Now that it has been shown that immunotherapy can be an effective cancer treatment, research is continuing to find new immune checkpoints and the possibility of combining targeted therapy with immunotherapy. Some believe that within the next ten years immunotherapy will constitute 60% of all cancer therapy.
Targeted therapies and immunotherapy continue to develop at an exponential rate and represent a unique approach to the treatment of cancer and will continue to do so in the next ten years.