STEPTRACKERPHARMACOLOGY + ONCOLOGY | ONCOLOGY | HIGH-YIELD REVIEW

Targeted Therapy & Antibodies

Targeted drugs hit a molecule the cancer depends on — a kinase, receptor or pathway — and the drug name usually tells you the class: -nib for small molecules, -mab for antibodies.

FOCUS ON
Tyrosine kinase inhibitors: imatinib (BCR-ABL, c-KIT → CML, GIST; edema, myelosuppression), dasatinib/nilotinib, erlotinib/osimertinib (EGFR → NSCLC; acneiform rash), vemurafenib/dabrafenib (BRAF V600E melanoma; + MEK inhibitor trametinib), crizotinib/alectinib (ALK), ibrutinib (BTK → CLL; bleeding, AF), ruxolitinib (JAK2 → myelofibrosis, PV). Antibodies: trastuzumab (HER2; reversible cardiotoxicity), rituximab (CD20; HBV reactivation, PML, infusion reactions), bevacizumab (VEGF; bleeding, GI perforation, poor wound healing, HTN, proteinuria), cetuximab/panitumumab (EGFR; KRAS wild-type colorectal; rash), daratumumab (CD38 myeloma). Checkpoint inhibitors: pembrolizumab, nivolumab (PD-1), atezolizumab (PD-L1), ipilimumab (CTLA-4) → immune-related adverse events (colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, type 1 DM, myocarditis) → steroids. Others: proteasome inhibitor bortezomib (neuropathy, zoster), all-trans retinoic acid/arsenic (APL; differentiation syndrome), PARP inhibitors (olaparib — BRCA), CDK4/6 (palbociclib), mTOR (everolimus), CAR-T (cytokine release syndrome → tocilizumab), hormonal agents (tamoxifen, aromatase inhibitors, leuprolide, enzalutamide).
DRUG
TARGET
CANCER
SIGNATURE TOXICITY
Imatinib · dasatinib · nilotinib
BCR-ABL, c-KIT, PDGFR
CML, Ph⁺ ALL, GIST
Fluid retention, myelosuppression; T315I resistance → ponatinib
Erlotinib · gefitinib · osimertinib
EGFR tyrosine kinase
EGFR-mutant NSCLC
Acneiform rash, diarrhea, interstitial lung disease
Vemurafenib · dabrafenib + trametinib
BRAF V600E · MEK
Melanoma, thyroid, hairy cell leukemia
Cutaneous squamous cell carcinomas (BRAF alone), photosensitivity
Ibrutinib · acalabrutinib
Bruton tyrosine kinase
CLL, mantle cell, Waldenström
Bleeding, atrial fibrillation, hypertension
Ruxolitinib
JAK1/2
Myelofibrosis, polycythemia vera, GVHD
Anemia, thrombocytopenia, infections
Trastuzumab · pertuzumab
HER2 (ERBB2)
HER2⁺ breast, gastric
Reversible cardiomyopathy (no dose-dependence; monitor EF)
Rituximab · obinutuzumab
CD20 on B cells
B-cell lymphomas, CLL; also RA, vasculitis, ITP
Infusion reactions, HBV reactivation, PML
Bevacizumab · ramucirumab
VEGF · VEGFR2
Colorectal, lung, renal, glioblastoma; wet macular degeneration
Hemorrhage, GI perforation, impaired wound healing, HTN, proteinuria, thrombosis
Cetuximab · panitumumab
EGFR (extracellular)
KRAS/NRAS wild-type colorectal, head and neck
Acneiform rash, ↓ Mg²⁺
Pembrolizumab · nivolumab · atezolizumab · ipilimumab
PD-1 · PD-L1 · CTLA-4 checkpoints
Melanoma, NSCLC, renal, MSI-high tumors, Hodgkin
Immune-related: colitis, hepatitis, pneumonitis, endocrinopathies, myocarditis
Bortezomib · carfilzomib
Proteasome inhibitors → misfolded protein buildup
Multiple myeloma, mantle cell
Peripheral neuropathy, zoster reactivation (give acyclovir)
All-trans retinoic acid · arsenic trioxide
Differentiate PML-RARα promyelocytes
Acute promyelocytic leukemia (t15;17)
Differentiation syndrome (fever, dyspnea, edema) → dexamethasone; arsenic QT
Olaparib · palbociclib · everolimus
PARP · CDK4/6 · mTOR
BRCA ovarian/breast/prostate · HR⁺ breast · renal, breast, TSC
Myelosuppression · neutropenia · stomatitis, hyperglycemia
CAR-T cells · blinatumomab
Engineered T cells (CD19, BCMA) · CD19/CD3 bispecific
Refractory B-cell ALL, lymphoma, myeloma
Cytokine release syndrome (tocilizumab), neurotoxicity (ICANS)

Mechanism — checkpoint blockade

Tumor expresses PD-L1
→
Binds PD-1 on T cellT cell switched off
→
Anti-PD-1 / PD-L1 antibodyT cell reactivated
→
Tumor killing — and autoimmunity

Name stems

STEM
MEANING
EXAMPLE
-tinib
Tyrosine kinase inhibitor
Imatinib
-ximab / -zumab / -umab
Chimeric / humanized / human antibody
Rituximab, trastuzumab, adalimumab
-zomib
Proteasome inhibitor
Bortezomib
-ciclib · -parib
CDK · PARP inhibitor
Palbociclib, olaparib

How it's tested

COMMON CONFUSIONTrastuzumab cardiotoxicity is usually reversible and not dose-related; anthracycline cardiotoxicity is cumulative and largely irreversible.
THE TRAPAnti-EGFR antibodies don't work in colorectal cancer with KRAS mutations — the pathway is switched on downstream of the receptor.
YOUR APPROACHMutation or marker → matching drug → class stem → signature toxicity → resistance mechanism.

If you see… think…

CML with t(9;22) → imatinib
GIST with c-KIT mutation → imatinib
Falling ejection fraction on HER2 therapy → trastuzumab
Bowel perforation and poor wound healing → bevacizumab
Acne-like rash on lung or colon cancer drug → EGFR inhibitor
Diarrhea, hepatitis or hypophysitis on immunotherapy → checkpoint inhibitor irAE → steroids
Hepatitis B flare after lymphoma antibody → rituximab
Fever, dyspnea, edema treating APL → differentiation syndrome
Neuropathy and shingles in myeloma treatment → bortezomib
Fever and hypotension after CAR-T infusion → cytokine release syndrome → tocilizumab