Targeted Therapy

Overview

Targeted therapy is a type of cancer treatment that focuses on attacking precise molecules or pathways critical to cancer cells’ growth and survival.

Unlike chemotherapy, a systemic treatment that affects both cancerous and healthy cells, targeted therapies are designed to interfere with features unique to cancer cells, minimizing the damage to normal or healthy cells and tissues. These therapies are often matched to your tumor profile through molecular profiling or genetic testing.

Cancer cells in the CSF can sometimes evade treatment because many chemotherapy drugs given by mouth or injected into a vein can’t cross into the CSF through the blood or through the brain itself. This natural protection system keeps harmful substances away from your brain. Intrathecal chemotherapy ensures the medicine can effectively reach and destroy these hidden cancer cells. Intrathecal chemotherapy can be administered via lumbar puncture or through a CSF reservoir-catheter system that is surgically placed under your scalp.

The advantage of targeted therapy is its precise action on cancer cell molecules or processes—hence the name. Because of its reduced impact on normal cells, it offers fewer side effects. It can be combined with other treatments, like radiation and chemotherapy, to maximize results. In other words, targeted therapy highly personalizes cancer treatments by tailoring them to a specific tumor: your tumor.

If your cancer’s molecular or genetic components qualify, targeted therapy treatments are available through your oncology team or through clinical trials. As part of the cancer research process, clinical trials determine if new treatments are safe, effective, or even better than the current standard. They can also be the best option for those with difficult-to-treat tumors to improve the odds of finding an effective treatment.

Barrow Neurological Institute is proud to be one of the country’s largest sites for neurological clinical trials in partnership with the Ivy Brain Tumor Center. Visit here to search for clinical trials that are now enrolling. 

The treatment will treat your cancer through one or more of the following mechanisms:

• Interrupting signals that trigger cancer cells to grow and divide: Some cancer cells have changes in their surface proteins that tell them to divide, whether or not the signals are really present. Certain targeted therapies can interfere with these protein changes, preventing them from telling the cells to divide and slowing down unchecked cancerous growth.
• Delivering cell-destroying substances to cancer cells: When particular targeted therapies are combined with cell-killing (cytotoxic) substances like chemotherapy or radiation, they can attach to targets on the surface of cancer cells. These cancer cells then take up the cytotoxic substances, leading to their death. Meanwhile, the cells that don’t have the target aren’t harmed.
• Cutting off the tumor’s blood supply: To grow beyond a specific size, tumors have to form new blood vessels through a process called angiogenesis. Some targeted therapies can interfere with these signals to prevent a blood supply from forming. Without a blood supply, tumors are unable to grow—and in the event one already exists, these therapies can cause blood vessels to die, causing the tumor to shrink. 
• Depriving cancer of the hormones it needs to grow: Some cancers, such as breast or prostate cancer, depend on hormones to grow. Targeted hormonal therapies can block hormone action in cancer cells in one of two ways: by preventing your body from making specific hormones or by blocking hormonal action on cells, including cancer cells.
• Causing cancer cell death: By design, healthy cells die when they are no longer needed or are damaged in a process called apoptosis. Unfortunately, cancer cells can avoid this process, so some targeted therapies work by triggering cell death.
• Activating the immune system: Much like immunotherapy, certain targeted therapies enhance the immune system’s ability to identify and destroy cancer cells by interfering with common immune checkpoint proteins. 

Typically, your tumor will need to be biopsied and tested to be eligible for targeted therapy. A biopsy establishes an exact diagnosis by surgically removing a small tissue sample or through stereotactic biopsy. Once a sample is taken, pathologists analyze the tissue under a microscope to determine the type of cells present and use molecular and biomarker testing to identify specific genetic mutations, overexpressed proteins, or other abnormalities. If your tumor is confirmed to have one or more of these, specific targeted therapies are identified.

Targeted therapies represent a long list of treatments, so medical professionals often categorize them by their mechanisms and the cancer targets they spotlight. That said, most targeted therapies fall into the category of monoclonal antibodies or small-molecule drugs.

• Monoclonal antibodies: These are large, lab-created proteins that attach to specific proteins on cancer cells or within their environment. Monoclonal antibodies can block cancer cell signals, flag cancer cells for destruction, or deliver toxins directly to the cancer cells. Examples of monoclonal antibodies include angiogenesis inhibitors, which block the formation of new blood vessels that tumors need to grow, and HER2-targeted agents that combat cancers that overexpress the HER2 protein.
• Small-molecule inhibitor drugs: These small compounds can enter cancer cells and interfere with or block specific enzymes or proteins involved in cancer cell growth. Examples of small-molecule inhibitor drugs include tyrosine kinase inhibitors (TKIs), which block enzymes involved in signaling pathways that regulate cell division; mTOR inhibitors, which disrupt a key protein for cell growth and proliferation; and PARP inhibitors, which make cancer cells more vulnerable to DNA damage.

Small-molecule drugs are pills or capsules you take orally, while monoclonal antibodies are typically given intravenously.

The duration of targeted therapy treatments also varies widely, depending on the type and stage of cancer and the specific drug used. For early-stage cancers, targeted therapies may be given for six months to one year and are often used in combination with surgery, chemotherapy, or radiation. For advanced or metastatic cancers, targeted therapy may continue indefinitely as long as the treatment remains effective and the side effects are manageable. Your doctor may stop treatments if the cancer progresses or if severe side effects occur.

If you’re using targeted therapy as a cancer treatment, your care team will monitor you closely through imaging and evolving tumor biomarkers, as well as the side effects you experience. If resistance to treatment emerges, a change in targeted therapy type may be required.

The current list of eligible cancers includes:

• Blood cancers like leukemia, lymphoma, and multiple myeloma.
• Brain cancers like glioblastoma and neuroblastoma.
• Breast cancers like HER2-positive breast cancer, BRCA gene mutation breast cancer, hormone receptor-positive breast cancer, and triple-negative breast cancer.
• Lung cancers like non-small cell lung cancer (NSCLC), small cell lung cancer, and mesothelioma.
• Reproductive cancers like cervical cancer, ovarian cancer, endometrial cancer, and prostate cancer.
• Digestive system cancers like colorectal cancer, esophageal cancer, gastrointestinal stromal tumors (GSIT), pancreatic cancer, stomach cancer, and liver cancer.
• Urinary cancers like bladder cancer, kidney cancer, and prostate cancer.
• Skin cancers like melanoma and cutaneous squamous cell skin cancer. 
• Thyroid cancers like anaplastic thyroid cancer and medullary thyroid cancers.

Targeted therapy has advanced cancer care by personalizing treatment options for certain cancers. Ultimately, targeted therapy’s success will depend on the type of cancer you have, the specific characteristics of your tumor, your overall health, and your response to treatment.