Anyone can get cancer at any age, although more than 90% of cancers are diagnosed in people 50 years and older. This is because the risk for cancer increases with age. Incidence rates also vary by gender, race and ethnicity. Although the number of deaths from cancer have reduced in the last few decades thanks to the development of new therapies, projections from the American Cancer Society suggest that there will be almost three new cancer diagnoses every minute, in 2018.
The majority of cancers are much more complicated in origin than most other diseases, and each one can have a molecular signature unique to a patient. Consequently, treating cancers can be an extremely entangled process compared to treating most other diseases. For centuries, surgery was the only option as a treatment for cancers. After Marie and Pierre Curie’s discoveries at the end of the 19th century, radiation became the next form of treatment. Towards the end of WWII, work by Goodman, Gilman and their coworkers at Yale University, resulted in the first recorded use of chemotherapy as a treatment for a cancer.
The National Cancer Institute lists more than 250 cancer drugs on its website – a few of these are targeted therapies. A targeted therapy is one that is designed to precisely “hit” only those cells that express the molecules that cause the cancer. In order to design a targeted therapy, a tremendous amount of research has to be done to understand the molecular mechanism that caused the cancer, and how the cancer cell survives and divides unceasingly. In the last two decades, due in large part to basic research funded by the National Institutes of Health, we now have access to targeted therapies to some cancers. The trailblazers were Herceptin, or trastuzumab, and Gleevec, or imatinib. In the US, Herceptin was approved for treatment of HER2+ breast cancers in 1998; Gleevec was approved for treating chronic myelogenous leukemia (CML) patients three years later.
A cell’s DNA might acquire mutations, some of which result in cancers, some of which become resistant to treatments. We’ve all heard of MRSA infections – those that are caused by staph bacteria that have become resistant to typical antibiotic treatments because of mutations in the staph DNA; tumor cells can similarly acquire a resistance to an ongoing therapy. Drug resistance can also occur because of other reasons, as shown below.
In some cases, tumors shrink significantly upon initial treatment with a targeted therapy, but the respite can be short-lived because the tumor develops resistance to the therapy. This can happen because the tumor exhibits a previously undetected mutation, which “outsmarts” the treatment program, resulting in the tumor growing again, and sometimes causing metastases in other organs. Scientists like Professor Politi and her research group, in conjunction with clinicians, are working tirelessly to understand the mechanisms underlying this process so as to nip drug resistance in the bud.
A relatively new addition to the possibilities for treating cancers is CAR-T therapy. Briefly, this involves getting the patient’s T-cells so that they can be engineered in the lab to express a specific protein on their surface, this will then help them to recognize tumor cells, and kill them. As of this writing, two CAR-T therapies have been approved by the FDA – one for acute lymphoblastic leukemia (ALL), the other for large-B-cell lymphomas. These are still early days of CAR-T therapies, with a promise for this method expanding to also treat other cancers.
Thank you, Professor Politi for giving us a broad understanding of cancer therapies – we left with a better appreciation for the enormous collaborative efforts needed to get to a point where drug resistance is not an impediment in curing cancers.