Fusion therapy is a form of targeted cancer treatment that goes after specific genetic abnormalities known as gene fusions. This approach is distinct from spinal fusion surgery, a procedure used to connect vertebrae in the spine. Instead, this therapy uses drugs to interfere with the molecular processes that allow specific cancer cells to grow and multiply, representing a personalized approach to cancer care.
The Science of Gene Fusions
Gene fusions are abnormal genes that form when two previously separate genes break and join together. This event is like mistakenly splicing together scenes from two different movie scripts, creating a new set of instructions that directs the cell to behave in unintended ways. This process can happen during cell division when chromosomes are rearranged incorrectly, resulting in hybrid genes that produce fusion proteins.
Fusion proteins are a factor in cancer development because they can act as a constant “on” switch for cell growth. In a healthy cell, growth signals are tightly regulated, telling the cell when to divide and when to stop. Fusion proteins override these controls by sending continuous signals that lead to the uncontrolled proliferation characteristic of cancer, making the cells dependent on the fusion protein for survival.
The presence of specific fusion genes helps in diagnosing and classifying certain types of cancer. Well-known examples include the BCR-ABL gene in chronic myeloid leukemia and the EML4-ALK gene in non-small cell lung cancer. While these fusions are common in some blood cancers, they are found less frequently in solid tumors. When identified in solid tumors, they become a clear target for therapy.
How Fusion Therapy Works
Fusion therapy uses drugs designed to block the activity of the fusion proteins driving cancer growth. These drugs are a class of medications called inhibitors, which are small molecules that can enter cells easily. The mechanism is precise, like a key made for a specific lock. The inhibitor drug is shaped to bind to the fusion protein’s active site, jamming it and preventing it from sending growth signals.
This specificity is what distinguishes fusion therapy from traditional chemotherapy. Because the drugs are tailored to an abnormality present only in cancer cells, they are less likely to harm healthy, normal cells. This targeted approach can lead to more effective treatment with potentially fewer severe side effects.
Examples of these therapies include TRK inhibitors, such as larotrectinib, which target NTRK gene fusions found across many tumor types. Another class is ALK inhibitors, which are used for cancers with an ALK gene fusion, most notably in a subset of non-small cell lung cancer patients. The development of these inhibitors is a direct result of understanding the genetic basis of certain cancers.
Identifying Candidates for Treatment
Determining who can benefit from fusion therapy requires sophisticated diagnostic testing, as it is only effective for patients whose tumors have a targetable gene fusion. A sample of the tumor tissue obtained through a biopsy is needed for biomarker testing. This analysis allows oncologists to practice personalized medicine by matching the patient to the most appropriate drug.
One of the most comprehensive methods used is Next-Generation Sequencing (NGS). This technology analyzes the tumor’s DNA and RNA to create a detailed map of its genetic landscape, identifying hundreds of potential gene fusions at once. This broad screening is useful because some fusions are rare and might otherwise be missed, revealing the exact genes that have fused together.
Another common testing method is Immunohistochemistry (IHC). This technique uses antibodies to detect the presence of the specific fusion protein within the tumor cells. If the fusion protein is being produced, the IHC test will show a positive result, indicating that the patient may be a candidate for a corresponding inhibitor drug.
The Treatment Regimen and Patient Experience
For most patients, fusion therapy is administered as an oral pill taken daily at home, which contrasts with intravenous chemotherapy that requires frequent clinic visits. The goal is to control the cancer long-term, and patients continue taking the medication for as long as it remains effective and side effects are manageable. Continuous treatment keeps the fusion protein’s growth signals turned off.
The patient experience with fusion therapy varies, and while targeted drugs spare many healthy cells, they can still cause adverse effects. Common side effects may include fatigue, dizziness, nausea, and changes in liver enzyme levels that require monitoring through regular blood tests. These effects can result from the inhibitor drug interacting with similar proteins in healthy cells.
Managing side effects is part of the overall treatment plan. Doctors work closely with patients to monitor their health and may adjust the dosage or provide supportive care to alleviate discomfort. The long-term nature of the treatment underscores the shift toward managing certain cancers as a chronic condition.