The Development of Targeted Therapy
The development of targeted therapies over the past 20 years has significantly changed how we treat cancer. These therapies are designed to focus on specific molecules that help cancer cells grow and survive. By targeting these exact processes, targeted therapies provide a more personalized approach to treatment, often working better and causing fewer side effects than traditional chemotherapy.
The use of targeted therapies depends on the type of cancer and its unique genetic makeup. For cancers with certain genetic mutations or changes, these therapies have become an important part of treatment. For example, in breast cancer, about 20-30% of patients now receive targeted therapies. In melanoma, where genetic mutations are more common, around 50-60% of patients may benefit from these advanced treatments.
These therapies are guided by biomarkers or genetic test results that help doctors choose the most effective treatment for each patient. As genomic testing and personalized medicine continue to improve, more types of cancer are being treated with targeted therapies, offering new hope and precision in cancer care
Types of Targeted Therapies
- Tyrosine Kinase Inhibitors (TKIs)– Tyrosine kinases are enzymes that regulate cell division, growth, and survival. In many cancers, these enzymes become overactive or mutated, causing uncontrolled cell growth. Tyrosine kinase inhibitors (TKIs) block these enzymes, disrupting the signals that promote cancer cell proliferation and survival. By inhibiting tyrosine kinases, TKIs can slow or stop cancer growth.
- Commonly used to treat: chronic myeloid leukemia (CML), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC)
- Drug names: imatinib (Gleevec), erlotinib (Tarceva), and sunitinib (Sutent).
- Monoclonal Antibodies (mAbs)– Monoclonal antibodies (mAbs) are lab-produced molecules designed to target specific antigens, such as proteins on cancer cells. They work by blocking signals that promote cell growth, flagging cancer cells for immune destruction, or delivering toxins directly to diseased cells.
- Commonly used to treat: Breast cancer, Leukemias, lymphomas, colorectal cancers, lung cancers, melanoma
- Drug names: Herceptin, Rituximab, Cetuximab, bevacizumab, ipilimumab
- Proteasome Inhibitors-A proteasome inhibitor is a type of cancer treatment that blocks the proteasome, a protein complex responsible for degrading unneeded or damaged proteins in cells. By inhibiting this process, these drugs cause a buildup of proteins within cancer cells, leading to cell stress and ultimately, cell death.
- Commonly used to treat: Multiple myeloma, lymphoma
- Drug names: Bortezomib (Velcade), Carfilzomib (Kyprolis), Ixazomib (Ninlaro)
- PARP Inhibitors-A PARP inhibitor is a type of cancer therapy that blocks the enzyme poly (ADP-ribose) polymerase (PARP), which helps repair DNA damage in cells. By inhibiting PARP, these drugs prevent cancer cells from repairing their damaged DNA, leading to cell death, particularly in tumors with existing DNA repair deficiencies. They are often used in cancers with BRCA1 or BRCA2 mutations.
- Commonly used to treat: Ovarian, breast, pancreatic, prostate,
- Drug names: Olaparib (Lynparza), Rucaparib (Rubraca), Niraparib (Zejula), Talazoparib (Talzenna)
- BRAF Inhibitors- A BRAF inhibitor is a type of targeted therapy that blocks the BRAF protein, which is involved in the MAPK/ERK signaling pathway that drives cell growth and division. Mutations in the BRAF gene, particularly the BRAF V600E mutation, can lead to uncontrolled cancer cell proliferation. By inhibiting this protein, BRAF inhibitors help slow down or stop the growth of cancer cells.
- Commonly used to treat: Melanoma, Non-small cell lung, thyroid cancers
- Drug names: Vemurafenib (Zelboraf), Dabrafenib (Tafinlar), encorafenib
- HER2 Inhibitors– A HER2 inhibitor is a targeted therapy that blocks the HER2 protein, a receptor that promotes cell growth and is overexpressed in some cancers. By inhibiting HER2, these drugs help slow down or stop the growth of cancer cells that rely on this protein for their proliferation. HER2 inhibitors are mainly used in cancers where HER2 is amplified or overexpressed.
- Commonly used to treat: Breast and gastric cancers
- Drug names: Trastuzumab (Herceptin), Pertuzumab (Perjeta), Lapatinib (Tykerb)
These examples highlight the diversity and specificity of targeted therapies, each designed to interfere with unique aspects of cancer biology, providing more personalized and effective treatment options. While this list highlights some of the key targeted therapies, it’s important to note that there are many more emerging treatments in the field. Advances in cancer research continue to drive the development of new and innovative therapies, expanding options for personalized treatment.
Impact on Cancer Treatment
Improved Survival and Quality of Life:
- Targeted therapies have led to significant improvements in overall survival and progression-free survival in patients with specific cancer types. For example, the introduction of TKIs like imatinib has turned CML into a chronic, manageable disease with high survival rates.
- The targeted nature of these therapies often results in fewer side effects compared to traditional chemotherapy, leading to a better quality of life for patients.
Personalized Medicine:
- The development of targeted therapies has opened the door to personalized cancer treatment. By pinpointing specific genetic mutations or markers in a patient’s tumor, doctors can create a treatment plan that is uniquely suited to the individual, making it more likely to be effective.
- The success of these therapies has also led to the creation of companion tests, which help doctors identify which patients are most likely to benefit from targeted treatments. This approach ensures that each patient gets the most appropriate and effective care for their specific type of cancer.
Resistance and Combination Therapies:
- Despite their success, resistance to targeted therapies can develop over time, leading to disease progression. This has spurred research into combination therapies, where targeted agents are combined with other treatments (e.g., chemotherapy, immunotherapy) to overcome resistance and improve outcomes.
- It is important for patients and clinicians to proactively plan in the face of anticipated resistance to ensure treatment remains effective and tailored to each patients evolving needs, which ultimately can improve outcomes and quality of life.
Expanding the Scope:
- Initially developed for a few cancer types, the application of targeted therapies has expanded to include a broad range of cancers. Advances in molecular biology and genomics have led to the discovery of new targets, enabling the development of novel targeted therapies for cancers previously lacking effective treatments.
The development of targeted therapies represents a significant leap forward in cancer treatment. These therapies have not only improved survival rates and quality of life for patients but have also ushered in an era of personalized medicine. While challenges such as drug resistance remain, ongoing research and the development of combination therapies continue to enhance the efficacy and applicability of targeted treatments across various cancer types.
About the Author
Dr. Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. With his many years of experience, he brings a wealth of expertise to the complex and challenging world of oncology. About Dr Thomas – MedOncMD