Making Cancer a Sitting Target

Cancer is personal on many levels. It is an attack on one’s life and family. It is an attack on the body from within. And it is a molecular attack, as the cancer cells arm themselves with genetic alterations that enable them to grow faster, live longer, and steal resources from normal, healthy cells that are just trying to do their jobs.

Every individual’s cancer is unique, with its own set of molecular abnormalities that distinguish it from everyone else’s. Such a uniquely individualized disease requires a personalized approach to combat it. And over the last two decades, a new era in cancer treatment has emerged to that end: targeted therapy.

What is targeted therapy?

Despite their unique molecular characteristics, most cancer cells have something in common: they grow more rapidly than other cells. That is why chemotherapy can be an effective cancer treatment – it broadly, and indiscriminately, kills fast growing cells (and also why people lose their hair while on chemotherapy, because hair follicle cells are fast growing!).

However, there are many different mechanisms cancer cells can use to grow, and different cancers use different mechanisms, or combinations of mechanisms, to thrive. Targeted therapies focus on the particular molecular changes in any given cancer cell that drive its growth, and they go for the jugular by directly attacking these changes, precisely and effectively halting cell growth. And, rapid advances in molecular diagnostics, including DNA and RNA sequencing methods, liquid biopsy technologies, and gene expression analysis techniques, have been a key partner in the development of targeted therapies. They have made it possible to decipher the specific molecular changes in an individual’s cancer cells. Identifying these changes is incredibly powerful, because they can now be matched with drugs that were born to target that exact change.

Types of targeted therapies

There are two main types of targeted therapies: 1) small molecule inhibitors; and 2) monoclonal antibodies. Small molecule inhibitors typically work inside the cancer cell, blocking signaling pathways that tell the cell to grow, grow, grow! Monoclonal antibodies typically work on the outside of the cells, stopping the signaling pathways from turning on in the first place. Both types of therapies can be very effective and are sometimes even used in combination for optimal effectiveness. Targeted therapies can also be used in combination with other types of cancer treatments, such as chemotherapy or immunotherapy, when a multipronged approach is warranted.

How many targeted therapies are there?

The first targeted therapy was approved by the FDA in 1997; it was a monoclonal antibody called rituximab (brand name Rituxan) and was used to treat B cell lymphoma. In 2001, the first small molecule inhibitor was approved for a certain type of leukemia; it was called imatinib mesylate, or Gleevec. In the two decades since, approximately 150 additional targeted small molecule inhibitor and monoclonal antibody therapies have been approved to treat all different types of cancers. They have revolutionized cancer treatment.

In our case study, Helping Henry Find His Quality of Life, we discuss how identifying a specific genetic mutation, called RET C630R, in Henry’s cancer enabled us to rapidly pivot from an ineffective treatment that was causing severe side effects to a personalized, targeted therapy that shrank his cancer and allowed him to enjoy good quality of life.

Targeted Resistance

While targeted therapies are designed to hit cancer cells in their Achilles heel, unfortunately the cancer cells can sometimes evolve to dodge their attack. They can acquire new alterations that provide them with a different, yet still menacing, growth advantage. In some cases, there is another targeted therapy already available that can target the resistant cells. In other cases, we may need to find another way to attack the cancer altogether.

That’s why it is important to always stay a few steps ahead. Using molecular diagnostics, we can interrogate how the cancer cells are growing. Then we can select therapies that target those growth pathways. This enables us to enlist our best line of defense every step of the way.