Whereas chemotherapy induces apoptosis by interfering with cell division of both cancerous and healthy cells, targeted therapy exploits targets, proteins, enzymes, or genes specific to malignant cells through a variety of mechanisms of action, which helps prevent drug resistance. The agents work by either inhibiting angiogenesis, blocking chemical signals that tell cells to divide or carry out normal function, or delivering toxic substances to a cell.
Extracellular Versus Intracellular
Some targeted agents capitalize on extracellular components of target receptors, and others work within the intracellular environment target to interfere with processes inside a malignant cell.
Extracellular targeted therapies: Tumor-associated antigens act as a beacon on the outer surface of cancer cells, calling attention to malignant cells for better specificity. Such activity has been likened to a “lock and key effect.” For a tumor-associated antigen to be most susceptible to targeted therapy, the antigen should be specific to cancer cells only, located on the surface of tumor cells, present in large numbers, and critical to tumor cell survival. Some monoclonal antibodies are classified as extracellular targeted therapies.
Intracellular targeted therapies: Other ways to alter and interfere with processes in malignant cells involve signal transduction or blood vessel formation that are directly involved in cancer cell proliferation and tumor growth. Examples of agents against these targets include EGFR inhibitors (e.g., cetuximab, erlotinib), HER2 inhibitors (e.g., trastuzumab, pertuzumab), and tyrosine kinase inhibitors (e.g., imatinib, dasatinib).
Side-Effect Profiles and Management
As with other pharmacologic therapies, expected side effects are related to the mechanism of action. Understanding how an agent works, the target it exploits, or the cellular process it interrupts speaks volumes about what we can expect our patients to experience and strategies to prevent complications.
For monoclonal antibodies—agents that end in “mab”—the nomenclature provides clinicians with indicators as to which side effects to anticipate. The middle of the generic name is indicative of its effects, lending insight into where to expect side effects. With pertuzumab or rituximab, the “tu” indicates the effect is right at the tumor and patients may experience pain at the tumor site. With bevacizumab, the “ci” indicates that the cardiovascular system is affected and patients can expect circulation disruption resulting in hypertension or impaired wound. See Figure 1 for more information about drug nomenclature.
Depending on the agent used, expected side effects can be an indicator that the drug is working and the therapy does not need to be altered. For example, with erlotinib, acute dermatologic reactions are expected and serve as an indicator that therapy is effective. A collaborative approach to interprofessional management and supportive care can ensure symptoms are controlled while allowing therapy to continue.
Many targeted agents, especially those working on intracellular activities, are given orally. ONS provides various resources to help clinicians promote oral adherence in their practice, including patient education videos and the Oral Adherence Toolkit.
Research suggests that using targeted therapies in combination with chemotherapy, radiation, and immunotherapy is most effective, and advancements in genetic profiling and molecular testing have allowed for better patient selection for targeted therapies. As we understand more about somatic genetic mutations and next-generation sequencing, we are better able to predict whether adding targeted therapies to treatment regimens will improve outcomes.
Nurses are becoming increasingly involved with educating patients and caregivers about the benefits and intricacies of targeted therapies, the role of genetic and tumor testing in determining a treatment plan, and the survivorship issues related to the agents.