Targeted Therapy for Cancer

Targeted Therapy for Cancer

Targeted therapy is a specialized approach to treating cancer that focuses on exploiting the characteristics of cancer cells while sparing healthy cells from damage. Unlike traditional chemotherapy, which can affect both cancerous and normal cells, targeted therapy aims to selectively disrupt the molecular pathways, proteins, or genetic mutations that contribute to the growth and survival of cancer cells.

How does targeted therapy work?

Targeted therapy for cancer patients works by exploiting specific molecular or genetic features that are unique to cancer cells. Targeted therapies are designed to interfere with these specific molecules or pathways, disrupting the cancer cell’s ability to grow and spread while minimizing damage to normal cells.

Let’s have a look at how targeted therapy works –

1. Identifying Molecular Targets – Before starting targeted therapy, the cancer cells are analyzed to identify specific genetic mutations, overexpressed proteins, or other molecular abnormalities that are contributing to the cancer’s growth. These molecular targets are often unique to the cancer cells or are present at higher levels in cancer cells compared to normal cells.

Targeted Therapy for Cancer

2. Developing Targeted Drugs – Once the molecular targets are identified, researchers develop drugs that are designed to interact with these specific targets. These drugs can take different forms, including small molecules and monoclonal antibodies.

• Small Molecule Inhibitors – These are small drugs that can enter cells and interfere with specific proteins or enzymes involved in cancer cell growth. They can work by blocking the activity of these proteins or enzymes, inhibiting signaling pathways that promote cell division and survival.
• Monoclonal Antibodies – These are large molecules that are designed to bind to specific proteins or receptors on the surface of cancer cells. By binding to these targets, monoclonal antibodies can block the signals that promote cancer cell growth, trigger an immune response against the cancer cells, or deliver toxic substances directly to the cancer cells.

3. Administering the Therapy – The targeted therapy drugs are administered to the patient through various methods, such as oral pills, intravenous infusions, or injections. The drugs then circulate in the bloodstream and reach the cancer cells.

4. Specific Interference – Once inside the cancer cells, targeted therapy drugs interfere with the molecular targets. This interference can involve –

• Blocking Signaling Pathways – Many targeted therapies work by inhibiting specific signaling pathways that are essential for cancer cell growth and survival. By disrupting these pathways, the drugs can slow down or stop the growth of cancer cells.
• Inducing Cell Death – Some targeted therapies can induce programmed cell death (apoptosis) in cancer cells, causing them to self-destruct.
• Starving the Tumor – Certain targeted therapies can cut off the blood supply to the tumor by targeting the molecules responsible for angiogenesis (the process of forming new blood vessels).

5. Monitoring and Adjusting Treatment – Patients undergoing targeted therapy are closely monitored to assess the effectiveness of the treatment. This may involve regular imaging scans, blood tests, and clinical evaluations. If the cancer responds well to the therapy, treatment may continue. If the cancer shows resistance or progression, treatment plans may need to be adjusted, potentially by switching to a different targeted therapy or combining therapies.

Prevent Tumor Resistance to Targeted Cancer Therapies

Preventing tumor resistance to targeted cancer therapies is a critical challenge in cancer treatment. Developing effective strategies to counteract resistance can improve treatment outcomes and extend patient survival.

Here are some strategies that researchers and clinicians employ to address this issue –

• Combining targeted therapies with other targeted agents, traditional chemotherapy, or immunotherapy can disrupt multiple pathways that cancer cells may use to develop resistance. This approach makes it harder for tumors to adapt and evolve resistance mechanisms.
• Administering multiple targeted therapies in sequence can help delay or prevent resistance. This involves starting with one targeted therapy and switching to another when resistance develops, effectively targeting multiple vulnerabilities.
• Continuously monitoring the genetic and molecular changes within a patient’s tumor can help adapt treatment strategies in real time. This personalized approach ensures that therapies are adjusted based on the evolving characteristics of the tumor.
• Tumors often consist of a mix of cells with different genetic and molecular profiles. Developing therapies that target multiple aspects of this heterogeneity can reduce the chances of resistance emerging.
• Combining targeted therapies with immunotherapies can enhance the immune system’s ability to recognize and attack cancer cells. This dual approach can prevent immune evasion and resistance.
• Developing methods to detect resistance mechanisms at an early stage can allow for timely adjustments to treatment plans. Liquid biopsies and other advanced diagnostics can help identify emerging resistance.
• Ensuring patients understand the importance of adhering to their treatment plans can minimize the chances of incomplete or irregular dosing, which can contribute to the development of resistance.

Using insights from evolutionary biology, treatments can be designed to slow down the evolution of resistant cancer cells by creating more barriers to adaptation.

Effectiveness of Targeted Cancer Therapies

Targeted cancer therapies offer numerous benefits that have significantly improved the landscape of cancer treatment. Some of these benefits include –

1. Precision Treatment – Targeted therapies focus on specific molecular alterations present in cancer cells, sparing healthy cells from damage. This precision leads to more effective treatment while minimizing side effects.
2. Enhanced Efficacy – By directly targeting critical molecules or pathways driving cancer growth, these therapies can result in higher response rates and tumor shrinkage, leading to improved outcomes.
3. Reduced Side Effects – Compared to traditional chemotherapy, targeted therapies cause fewer and less severe side effects, enhancing patients’ quality of life during treatment.
4. Combination Potential – Many targeted therapies can be combined with other treatment modalities, such as immunotherapy or chemotherapy, to synergistically attack cancer cells on multiple fronts, reducing the risk of resistance.
5. Improved Survival – In certain cancers with well-defined molecular targets, targeted therapies have led to extended overall survival rates and increased progression-free survival.
6. Addressing Resistance – Researchers are working to understand and counter mechanisms of resistance, ensuring that targeted therapies remain effective over time.
7. Positive Impact on Healthcare Costs – Despite potential high upfront costs, targeted therapies can reduce long-term healthcare costs by minimizing hospitalizations and managing side effects.
8. Innovative Research – The development of targeted therapies has spurred innovative research into cancer biology, leading to deeper insights and advancements in the field.

Types of Target Molecular Therapy

Targeted molecular therapy encompasses various approaches that specifically target key molecules, proteins, or pathways involved in cancer growth and survival. Some common types of targeted molecular therapies include –

1. Tyrosine Kinase Inhibitors (TKIs) – These drugs block the activity of tyrosine kinases, which are enzymes that play a role in cell signaling and growth. TKIs are used to target specific receptors or proteins that are overactive in cancer cells. Examples are – imatinib for chronic myeloid leukemia (CML) and EGFR inhibitors for lung and colorectal cancers.
2. Monoclonal Antibodies – Monoclonal antibodies are engineered proteins that bind to specific targets on cancer cells. They can either directly inhibit cell growth or tag cancer cells for destruction by the immune system. Examples are – trastuzumab for HER2-positive breast cancer and rituximab for certain types of lymphoma.
3. Angiogenesis Inhibitors – These drugs target the process of angiogenesis, where new blood vessels form to supply nutrients to tumors. By inhibiting this process, they can limit the tumor’s blood supply and growth. Bevacizumab is an example used in various cancers.
4. Hormone Therapy – Hormone therapy is used to treat hormone-sensitive cancers like breast and prostate cancer. It involves blocking or lowering the levels of hormones that fuel cancer growth. Examples are – tamoxifen for estrogen receptor-positive breast cancer and androgen deprivation therapy for prostate cancer.
5. Proteasome Inhibitors – These drugs interfere with the proteasome, a cellular complex that breaks down proteins. By inhibiting proteasomes, these drugs disrupt the normal protein degradation process in cancer cells, leading to their death. Bortezomib is an example used in multiple myeloma.
6. PARP Inhibitors – These inhibitors target poly(ADP-ribose) polymerase (PARP) enzymes, which play a role in DNA repair. They are particularly effective in cancers with BRCA gene mutations, as cancer cells with these mutations are more sensitive to DNA damage. Olaparib is an example used in ovarian and breast cancers.
7. Immunotherapy – While not traditional molecular therapy, immunotherapy targets the immune system to attack cancer cells. Checkpoint inhibitors like pembrolizumab and nivolumab block proteins that inhibit immune responses, allowing the immune system to target cancer cells.
8. Signal Transduction Inhibitors – These drugs interfere with signaling pathways within cancer cells that regulate growth, survival, and other functions. Examples include BRAF inhibitors for BRAF-mutated melanoma and HER2-targeted therapies for HER2-positive breast cancer.
9. Multikinase Inhibitors – These inhibitors target multiple kinases at once, often used when cancers have several pathways driving their growth. Sorafenib and sunitinib are examples used in kidney cancer and certain types of leukemia.
10. Epigenetic Modulators – These drugs alter the epigenetic modifications of genes, affecting how genes are expressed. They can impact cancer growth by changing gene activity. Examples include DNA methyltransferase inhibitors like azacitidine.

What type of cancer is targeted therapy used for?

Targeted therapy is used for a wide range of cancer types, but its effectiveness often depends on the specific molecular alterations driving the growth of the cancer cells. Some of the cancer types for which targeted therapy has been developed and utilized include –

• Breast Cancer
• Lung Cancer
• Colorectal Cancer
• Leukemia
• Melanoma
• Gastrointestinal Stromal Tumors (GIST)
• Ovarian Cancer
• Lymphomas
• Prostate Cancer
• Thyroid Cancer
• Neuroblastoma
• Multiple Myeloma

These are just a few examples, and new targeted therapies continue to be developed for various cancer types as our understanding of cancer biology deepens. Targeted therapy is typically tailored to the specific genetic and molecular characteristics of the cancer, allowing for more precise and effective treatment strategies.

When is targeted therapy given to cancer patient?

Targeted therapy is given to cancer patients when their tumors have specific molecular alterations that can be targeted by these therapies. The decision to administer targeted therapy is based on a combination of factors, including the type of cancer, the presence of specific genetic or molecular markers, the patient’s overall health, and the stage of the disease. 

Molecular Testing – Before targeted therapy is considered, molecular testing is performed on the patient’s tumor tissue or, in some cases, through liquid biopsies. These tests identify genetic mutations, amplifications, or overexpressed proteins that are characteristic of the cancer. The presence of these molecular alterations determines whether the patient is a candidate for targeted therapy.

Type of Cancer – Different types of cancer have specific targeted therapies. For instance, HER2-targeted therapies are used in HER2-positive breast cancer, while BRAF inhibitors are employed for certain melanomas. The type of cancer guides the choice of targeted therapy.

Treatment Stage – Targeted therapy can be used at various stages of cancer treatment. It can be a first-line treatment (initial therapy), a second-line treatment (after initial treatment), or even used in combination with other therapies, such as chemotherapy or immunotherapy.

Patient’s Overall Health – The patient’s overall health and medical history are important factors in determining the appropriateness of targeted therapy. Patients with certain medical conditions or comorbidities might need careful evaluation before starting treatment.

Clinical Trials

Many clinical trials of targeted therapy follow a randomized controlled design, where patients are randomly assigned to receive the targeted therapy or a comparator treatment. This helps eliminate bias and provides more reliable results. Some trials investigate the efficacy of combining targeted therapies with other treatments, such as chemotherapy, immunotherapy, or radiation therapy, to enhance treatment outcomes.