Understanding Targeted Therapy
Cancer treatment has changed more in the past two decades than it has ever before. One of the developments sitting at the centre of that change is targeted therapy, a treatment approach that has fundamentally altered what is possible for patients with certain types of cancer. It is increasingly part of conversations in oncology clinics, and yet for most patients, what it actually means and how it differs from conventional treatment remains unclear.
Understanding what targeted therapy for cancer does, and why it matters, helps patients make sense of what their oncologist is recommending and why.
The problem with conventional chemotherapy
To understand why targeted therapy represents a shift in approach, it helps to first understand the limitation it was developed to address. Conventional chemotherapy works by killing rapidly dividing cells. Cancer cells divide rapidly, so chemotherapy impacts them. The problem is that many healthy cells in the body also divide rapidly, including those lining the digestive tract, the hair follicles, and the bone marrow. This is why chemotherapy produces the side effects it does. It cannot distinguish between cancer cells and healthy cells that happen to share the same property.
Traditional chemotherapy can damage both cancerous and healthy cells. The targeted therapy drugs are designed to target specific cancer-related targets and are therefore less harmful to healthy cells, resulting in better effects on the cancer and a lower risk of side effects for most patients.
How targeted therapy works
Targeted therapy is cancer treatment that targets the genetic changes or mutations that turn healthy cells into cancer cells. Oncologists use information on the unique genetic alterations or mutations in the tumour to choose treatment that targets the unique components of cancer cells that these changes activate.
Cancer cells sustain and grow due to certain molecular dysfunctions. A protein that signals a cell to keep dividing when it should stop. An enzyme that helps the tumour build new blood vessels to feed itself. A receptor that, when activated, allows cancer cells to evade the immune system. The mechanism of action of targeted therapy is to interrupt the specific malfunction, instead of indiscriminately attacking all dividing cells.
Specific molecules that are involved in cancer or single oncogenic drivers can be targeted to prevent cell growth. These have changed cancer care by tailoring treatment to an individual patient's tumour characteristics and improving outcomes.
Types of targeted therapy
Targeted therapy covers a broad category of treatments, each working through a different mechanism depending on what molecular target is involved.
Small-molecule inhibitors are medications that can be taken into the cell and affect proteins within the cell. They are usually given in tablet or capsule form and act by preventing the signals which stimulate the growth and division of cancer cells. They are employed in cancers like some lung cancers, leukaemia, gastrointestinal cancers, etc.
Monoclonal antibodies are laboratory-produced proteins that bind to and recognise certain parts of the cancer cell surface. Once attached, they can block signals, flag the cell for destruction by the immune system, or deliver toxic substances directly to the cancer cell. HER2-positive breast cancer is one of the most well-known examples where monoclonal antibodies have transformed outcomes.
Angiogenesis inhibitors block the formation of new blood vessels that tumours need to grow. Without a blood supply, tumours cannot sustain growth beyond a certain size.
Targeted therapy vs chemotherapy
The distinction between targeted therapy vs chemotherapy is not that one is better than the other in all situations. They work through fundamentally different mechanisms and are suited to different circumstances.
Chemotherapy remains effective for many cancer types, particularly where no specific targetable mutation has been identified, or where the cancer is broadly sensitive to cell-killing agents. Targeted therapy works most reliably when a specific molecular target is present in a patient's tumour, which is why genetic testing of the tumour is a necessary first step before targeted treatment can be selected.
The two approaches are increasingly used together, with targeted therapy added to chemotherapy regimens to improve response rates, or used sequentially depending on how the disease responds over time.
Why tumour testing matters
Targeted therapy is only effective when the target it is designed to attack is actually present in the patient's cancer. This is why molecular profiling of the tumour, often through a biopsy or liquid biopsy, is now a standard part of treatment planning for many cancer types.
Each patient responds to targeted therapy differently due to their unique genomic profile. Next-generation sequencers have helped narrow the gap between sequencing and precision medicine and helped identify more targets for action.
Treatment may be very different for two patients with the same type of cancer, depending on their tumour molecular profile. This is what precision medicine cancer treatment means in practice. The treatment is matched to the biology of the individual tumour, rather than applied uniformly based on where in the body the cancer originates.
Resistance to targeted therapy
One of the ongoing challenges with targeted therapy is that cancers can develop resistance over time. If a targeted drug interferes with one growth pathway, some cancer cells may have other pathways to grow. That is why oncologists carefully watch how well the treatment is working, frequently using repeat imaging or liquid biopsies, and tweak the treatment plan when resistance arises. One approach to minimise the risk of resistance developing is to use targeted agents in conjunction with other methods of treatment.
Takeaways
Targeted therapy cancer treatment targets and attacks the specific molecular abnormalities that drive a specific tumour, instead of indiscriminately killing all rapidly growing cells. The mode of action of targeted therapy varies according to the drug used and the molecular target, which includes small molecule inhibitors, monoclonal antibodies and angiogenesis inhibitors.
The comparison of targeted therapy vs chemotherapy is not one of superiority but rather different mechanisms fit to different situations. Precision medicine cancer treatment begins with tumour testing, which determines whether a targetable mutation is present and guides which treatment is most likely to be effective.