8. TARGETED THERAPIES FOR CANCER

Targeted therapy

is a cornerstone of precision medicine. It directs treatment based on the specific genes or proteins that control how cancer cells grow, divide, and multiply

Targeted therapies

Specific, deliberate, and often cytostatic (stop cancer cell growth/division). They aim to interfere with specific molecular pathways crucial for cancer.

Chemotherapies

Not specific; cytotoxic (kill) to both normal and abnormal cells. They typically act by damaging DNA or interfering with cell division in a broad manner

-mab

indicates a monoclonal antibody

-inib

indicates a tyrosine kinase inhibitor

-zomib

indicates a proteasome inhibitor

Small-molecule drugs

TYPES OF TARGETED THERAPIES

these drugs have a small size, making it easy for them to enter cells and target intracellular molecules. They block cancer cells from multiplying and spreading by targeting specific proteins on the inside of the cell. They can inhibit enzymes, block the formation of new blood vessels, and induce apoptosis (programmed cell death)

Angiogenesis Inhibitors

Small-molecule drugs

• Mechanism of Action: Block the growth of new blood vessels (angiogenesis) that tumors need to grow and spread. Tumors require a robust blood supply to deliver nutrients and oxygen. By inhibiting this process, angiogenesis inhibitors "starve" the cancer cells, preventing them from getting their supply of nutrients.

• Vascular Endothelial Growth Factor/Receptor Inhibitors (VEGF/VEGFR Inhibitors): These agents specifically inhibit the activity of VEGF (a protein that promotes blood vessel growth) and its receptors

Bevacizumab (Avastin)- Angiogenesis Inhibitors

• Mechanism of Action: A recombinant humanized monoclonal antibody that directly binds to and neutralizes Vascular Endothelial Growth Factor (VEGF). By preventing VEGF from binding to its receptors on endothelial cells, bevacizumab inhibits the formation of new blood vessels and reduces the vascularization of tumors.

• Route: IV.

• Indications: Management of cervical, colorectal, and ovarian cancers; metastatic renal cell carcinoma (RCC); non-small cell lung cancer (NSCLC); and relapsed glioblastoma multiforme.

• Side Effects (SE): Hypertension, proteinuria, headache (cephalgia), rhinitis, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

• Adverse Reactions (AR): Perforation of the gastrointestinal tract, fistula formation, thromboembolic events (blood clots), hypertensive crisis/encephalopathy, nephrotic syndrome, infusion reactions, embryonic/fetal toxicity, ovarian failure, Posterior Reversible Encephalopathy Syndrome (PRES), exogenous endophthalmitis, gallbladder perforation, and congestive heart failure.

• Contraindications: Known murine hypersensitivity (allergy to mouse proteins), hamster protein hypersensitivity, or hypersensitivity to any other component of the drug; pre-existing hypertension, cardiovascular disease, renal disease, history of glaucoma.

Epidermal Growth Factor/Receptor Inhibitors (EGFR Inhibitors)

Small-molecule drugs

Mechanism of Action: These drugs bind to different areas of the Epidermal Growth Factor Receptor (EGFR) on cancer cells, which then blocks its activity to activate Tyrosine Kinase. EGFR signaling promotes cell growth and proliferation in many cancers

Osimertinib (Tagrisso)- Epidermal Growth Factor/Receptor Inhibitors (EGFR Inhibitors)

• Mechanism of Action: A third-generation EGFR tyrosine kinase inhibitor (TKI) that selectively and irreversibly inhibits certain EGFR mutations (T790M and activating EGFR mutations) that drive cancer growth. By blocking EGFR signaling, it inhibits cancer cell proliferation and promotes apoptosis.

• Route: Oral.

• Indications: Used to manage NSCLC, particularly in patients with specific EGFR mutations.

• SE: Pancytopenia (reduction in all blood cell types), rash, dry skin, anorexia, constipation, hyponatremia, nausea, pruritus (itching), fatigue, cough, back pain, and stomatitis (mouth sores); eye disorders and headache (cephalgia).

• AR: Venous thromboembolism, interstitial lung disease (ILD), pneumonitis (inflammation of lung tissue), increased QTc interval (cardiac rhythm abnormality), cardiomyopathy (heart muscle disease).

• Contraindications: Patients with pre-existing interstitial lung disease/pneumonitis and symptomatic heart failure.

Tyrosine Kinase Inhibitors (TKIs) / Signal Transduction Inhibitors

Small-molecule drugs

• Mechanism of Action: Tyrosine kinases are enzymes that act like a cell’s on and off switch for growth signals. TKIs block these enzymes from sending signals that cause a cancer cell to grow or multiply. They are among the most common targeted therapies.

• Multikinase Inhibitors: These are a subset of TKIs that directly obstruct the activity of multiple specific kinases in cancer cells as well as those involved in forming cancer cell vasculature.

Alectinib (Alecensa)-Tyrosine Kinase Inhibitors (TKIs) / Signal Transduction Inhibitors

• Mechanism of Action: A highly selective ATP-competitive inhibitor of Anaplastic Lymphoma Kinase (ALK) and RET kinases. It binds to and inhibits these kinases, disrupting the signaling pathways that promote cell growth and survival in cancers driven by ALK fusions (e.g., in NSCLC).

• Route: Oral.

• Indications: Indicated for ALK-positive metastatic NSCLC in a patient who has progressed on or is intolerant to crizotinib (another ALK inhibitor).

• SE: Anemia, elevated transaminases (liver enzymes), fatigue, constipation, bradycardia (slow heart rate), edema (swelling), hypocalcemia, hypokalemia, and myalgia (muscle pain).

• AR: Hepatotoxicity (liver damage), pneumonitis (lung inflammation), bradycardia, and elevated creatine phosphokinase (CPK - indicating muscle damage)

mTOR Kinase Inhibitors

Small-molecule drugs

Mechanism of Action: mTOR (mammalian Target of Rapamycin) is an atypical serine/threonine protein kinase that helps regulate cell growth, proliferation, and survival. Inhibitors of mTOR lead to G1 cell cycle arrest (preventing cells from moving into the S phase) and induce apoptosis.

Temsirolimus (Torisel)- mTOR Kinase Inhibitors

• Mechanism of Action: An inhibitor of mTOR. It binds to FKBP-12 (FK506-binding protein), and this complex inhibits mTOR. By inhibiting mTOR, temsirolimus blocks downstream signaling pathways involved in cell growth, proliferation, and angiogenesis, leading to cell cycle arrest and apoptosis.

• Route: IV.

• Indications: Commonly used to treat advanced RCC.

• SE: Hypersensitivity (pre-medicate with an IV antihistamine), weakness, rash, mucositis, nausea, edema, anorexia, dyspnea (shortness of breath), pain, elevated transaminases, pancytopenia, hyperlipidemia, diarrhea, hypophosphatemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia (may require antidiabetic agents or insulin).

• AR: Respiratory adverse effects (e.g., pneumonitis), liver & renal impairment, cardiovascular effects of edema formation, chest pain, hypertension, venous thromboembolism, thrombophlebitis.

• Contraindications: Moderate to severe hepatic impairment.

Proteasome Inhibitors

Small-molecule drugs

Mechanism of Action: Proteasomes are protein complexes within cells that degrade unwanted or damaged proteins (e.g., those that trigger cell division, or those that promote cell survival by inhibiting apoptosis). Proteasome inhibitors block the action of proteasomes, preventing them from eating up these excess/damaged proteins. This leads to an accumulation of abnormal proteins within cancer cells, triggering cellular stress responses, cell cycle arrest, and ultimately apoptosis

Bortezomib (Velcade)- Proteasome Inhibitors

• Mechanism of Action: A reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. By inhibiting proteasome function, it interferes with numerous cellular processes, including protein degradation, cell cycle progression, and cell survival, leading to apoptosis in cancer cells.

• Route: IV or Subcutaneous (SQ).

• Indications: Commonly used to treat mantle cell lymphoma (MCL) and multiple myeloma.

• SE: Nausea, vomiting, diarrhea, constipation, anorexia, abdominal pain, dyspepsia (indigestion), dysgeusia (taste alteration), hypotension (low blood pressure), neuropathy (nerve damage), pancytopenia, rash, urticaria (hives), vasculitis (inflammation of blood vessels), pruritus, injection site reaction, arthralgia (joint pain), myalgia (muscle pain), back pain, bone pain, bone fractures, hyperglycemia, hypoglycemia, fatigue, fever, insomnia.

• AR: Severe sensory and peripheral neuropathy (can be dose-limiting), cardiotoxicity (heart damage), heart failure, QT prolongation (cardiac rhythm abnormality), arrhythmias, pulmonary hypertension, acute respiratory distress syndrome (ARDS), pneumonitis, interstitial pneumonia, GI perforation, GI toxicity (e.g., hemorrhage), hepatotoxicity, toxic epidermal necrolysis (TEN - severe skin reaction), acute febrile neutrophilic dermatosis (Sweet syndrome).

• Contraindications: Intrathecal administration (NEVER administer intrathecally as it is fatal); patients with mannitol, bortezomib, or boron hypersensitivity; avoid during pregnancy; breastfeeding should be discontinued; caution in patients with cardiac, pulmonary, and liver disorders; bleeding dyscrasias; pancytopenia; dehydration; diabetes mellitus; herpes infection; active bleeding; history of tumor lysis syndrome; neonates and children.

Monoclonal antibodies (MAbs)

TYPES OF TARGETED THERAPIES

these are proteins produced in the lab that imitate the body’s natural immune system to fight off cancer. They are engineered to specifically bind to targets (antigens) on cancer cells or on immune cells to modulate their activity

Cetuximab (Erbitux)- Monoclonal antibodies (MAbs)

• Mechanism of Action: A chimeric (mouse-human) monoclonal antibody that specifically binds to the extracellular domain of the Epidermal Growth Factor Receptor (EGFR). By blocking EGFR, it prevents the binding of EGF and other ligands, thereby inhibiting EGFR-mediated signaling pathways that promote cancer cell growth, proliferation, and survival. It can also mediate antibody-dependent cell-mediated cytotoxicity (ADCC).

• Route: IV.

• Indications: For colorectal and head and neck cancers.

• SE/AR: Infusion reactions with manifestations of rapid onset of airway obstruction (bronchospasms, stridor, hoarseness, urticaria, hypotension); dermatologic changes usually in the face, upper chest, and back (acneiform rash, a common and often severity-related side effect).

• Contraindications: Use with cisplatin and radiation therapy in certain settings may increase the incidence of adverse events (e.g., mucositis). History of severe hypersensitivity reaction to cetuximab.

NURSING PROCESS (Targeted Therapies for Cancer)

Assessment (A):

• Avoid drug interactions: Obtain a detailed medication history (prescription, OTC, herbal supplements), and assess for drug and food allergies.

• Obtain baseline information about the patient’s physical status (e.g., vital signs, weight, general condition) and baseline laboratory values (e.g., CBC with differential, electrolytes, renal and liver function tests).

• Assess results of specific tests relevant to the targeted therapy (e.g., Pulmonary Function Tests [PFTs], Creatinine Clearance [CrCl], Electrocardiogram [ECG], and detailed renal and liver function studies).

• Assess the patient’s and caregiver’s current level of comprehension related to the therapeutic regimen, including understanding of the disease, treatment, side effects, and self-care.

Diagnosis (D):

• Risk for Impaired Skin Integrity (due to dermatologic reactions).

• Risk for Infection related to bone marrow suppression (neutropenia).

• Deficient Knowledge related to the targeted therapy regimen (medication administration, side effects, self-care).

• Risk for Injury related to toxic effects of targeted therapy (e.g., cardiotoxicity, nephrotoxicity, neurotoxicity).

• Risk for Disturbed Sensory Perception (e.g., visual disturbances, peripheral neuropathy).

Planning (P):

• Patient will maintain skin integrity and remain free from infection.

• Patient and family/caregivers will be educated about the targeted therapy as part of the anticancer treatment regimen, strategies to minimize its side effects, and the importance of reporting these side effects and adverse reactions.

• Side effects will be managed to a tolerable level and are not life-threatening.

Interventions (I):

• Examine the patient’s skin closely and rate the severity of dermatologic reactions (e.g., acneiform rash, dryness, nail changes). Implement skin care protocols.

• Monitor liver function tests (LFTs) and renal function tests (RFTs) at baseline and at least once a month (or more frequently per protocol).

• Monitor other relevant laboratory values according to established protocols for specific targeted therapies (e.g., CBC, electrolytes, cardiac biomarkers, blood glucose).

• Administer prescribed premedications (e.g., antihistamines for infusion reactions) according to established protocols.

• Assess for any cardiac events (e.g., arrhythmias, heart failure symptoms); have resuscitative equipment on standby as per protocol, especially for drugs with known cardiotoxicity.

• Ensure appropriate supervising personnel (e.g., physician, trained nurse) are present during initial infusions and for drugs with a high risk of adverse reactions.

Patient Teaching:

• Report symptoms of bleeding immediately (e.g., unusual bruising, petechiae, blood in urine/stool, nosebleeds, prolonged bleeding from cuts).

• Report symptoms of adverse effects or severe side effects promptly (e.g., severe rash, shortness of breath, chest pain, vision changes, severe diarrhea, persistent vomiting, fever).

• Report signs of liver impairment immediately (e.g., yellowing of skin/eyes, dark urine, severe fatigue, right upper quadrant pain).

• Avoid alcohol and nonessential drugs that are cleared by the liver or have hepatotoxic effects, as they can exacerbate liver toxicity.

• For women of childbearing potential: Advise to avoid getting pregnant throughout treatment and for up to 12 months after treatment is completed, due to potential embryonic/fetal toxicity. Use effective contraception.

• For breastfeeding patients: Advise to stop breastfeeding during and for at least 60 days after therapy, due to potential drug excretion in breast milk.

• For diabetic patients: Advise to monitor blood glucose more frequently, as some targeted therapies can cause hyperglycemia or hypoglycemia, and advise when to seek medical help for blood sugar control issues.

• Immediately report neurological symptoms such as convulsions, persistent headache, reduced eyesight, increased blood pressure, or blurred vision (e.g., indicative of PRES, hypertensive crisis).

• Emphasize proper waste disposal for patients receiving monoclonal antibodies (and other cytotoxic drugs) to prevent unnecessary exposure to others (e.g., flush body fluids, double bag contaminated waste).

Evaluation (E):

• Patient, family, and caregiver education needs are met, indicating understanding of the therapy.

• Patient, family, and caregivers understand therapy-related side effects/adverse reactions and strategies to minimize them.

• Side effects are managed effectively, and the patient is free from infection.

• Patient’s fluid balance and electrolytes are maintained at expected normal ranges.

• Achievement of therapeutic goals (e.g., tumor shrinkage, stable disease, improved quality of life).

Drawbacks of Targeted Therapies: Resistance

Cancer cells can become resistant to targeted therapies over time through new mutations or activation of alternative signaling pathways

Drawbacks of Targeted Therapies: Development Complexity

Some drugs for targeted therapies are hard to develop due to the specificity required for their targets and the challenges in identifying actionable mutations in diverse cancer types.