Core Oncology Concepts for Step 1
Step 1 oncology questions heavily emphasize the molecular and cellular basis of cancer development. You need to understand the two-hit hypothesis, which explains how both copies of a tumor suppressor gene must be inactivated for cancer to develop.
Tumor Suppressors and Oncogenes
This concept applies to classic conditions like retinoblastoma and Li-Fraumeni syndrome. Equally important is recognizing oncogenes and their mechanisms: RAS mutations in colorectal cancer, MYC translocation in Burkitt lymphoma, and BCR-ABL fusion in chronic myeloid leukemia. Step 1 expects you to know the Philadelphia chromosome (9;22 translocation) and its significance.
Viral Oncogenesis
Familiarize yourself with the Knudson multi-hit model and how it explains familial cancer syndromes. Additionally, understand the role of viral oncogenesis: HPV in cervical cancer, HBV in hepatocellular carcinoma, and EBV in Burkitt lymphoma and nasopharyngeal carcinoma. The exam frequently tests your ability to connect genetic abnormalities to specific malignancies.
Key Cellular Processes
You should also grasp basic concepts like angiogenesis, metastasis, and epithelial-mesenchymal transition (EMT). These foundational principles appear across multiple question stems and help you reason through unfamiliar scenarios.
High-Yield Cancer Types and Presentations
Certain cancers appear disproportionately on Step 1 because they have distinctive presentations, classic associations, and important treatment implications.
Gastrointestinal and Lung Cancers
Colorectal cancer requires knowledge of the adenoma-carcinoma sequence, Lynch syndrome, and familial adenomatous polyposis (FAP). Lung cancer questions often focus on small cell lung cancer (SCLC) versus non-small cell lung cancer (NSCLC). Know their molecular drivers: EGFR, ALK, and KRAS mutations. SCLC commonly presents with paraneoplastic syndromes like SIADH.
Breast and Reproductive Cancers
Breast cancer questions test your understanding of HER2 amplification, estrogen receptor status, and BRCA mutations. Ovarian cancer frequently appears with questions about BRCA1/BRCA2 mutations and PARP inhibitor mechanism.
Hematologic and Solid Malignancies
Leukemias and lymphomas are extremely common on Step 1: distinguish between acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Recognize Hodgkin versus non-Hodgkin lymphoma characteristics. Know key prognostic markers for each. Testicular cancer questions emphasize germ cell tumors and tumor markers: AFP, beta-hCG, and LDH.
Other High-Yield Cancers
Melanoma appears frequently with questions about BRAF mutations and checkpoint inhibitor immunotherapy. Renal cell carcinoma (clear cell type) requires knowledge of VHL gene mutations. Additionally, know classic presentations: Wilms tumor in young children, rhabdomyosarcoma in soft tissues, and osteosarcoma around the knee in adolescents. Each cancer type has associated symptoms, staging patterns, and treatment regimens you must memorize.
Chemotherapy Mechanisms and Drug-Specific Toxicities
Step 1 dedicates significant content to chemotherapy classification and mechanism of action. Organize drugs by category to maximize retention and recall speed.
Alkylating Agents and Platinum Compounds
Alkylating agents (cyclophosphamide, cisplatin) cross-link DNA. You must know that cyclophosphamide causes hemorrhagic cystitis and cisplatin causes nephrotoxicity and ototoxicity. Platinum agents require aggressive hydration and mesna for hemorrhagic cystitis prevention.
Antimetabolites and Topoisomerase Inhibitors
Methotrexate inhibits dihydrofolate reductase and requires leucovorin rescue. 5-fluorouracil inhibits thymidylate synthase and causes hand-foot syndrome. Topoisomerase inhibitors (etoposide, irinotecan, topotecan) cause bone marrow suppression. Irinotecan specifically causes delayed diarrhea.
Taxanes, Vinca Alkaloids, and Bleomycin
Taxanes (paclitaxel, docetaxel) cause peripheral neuropathy. Paclitaxel requires Cremophor EL premedication. Vinca alkaloids cause peripheral neuropathy and are vesicants. Bleomycin causes pulmonary fibrosis and requires baseline and regular pulmonary function tests.
Anthracyclines and Targeted Agents
Anthracyclines (doxorubicin) cause dose-dependent cardiomyopathy. Require baseline echocardiogram and monitoring. Dexrazoxane can prevent anthracycline cardiomyopathy. HER2-targeted therapy (trastuzumab) also causes cardiomyopathy. Tyrosine kinase inhibitors like imatinib target BCR-ABL in CML with excellent outcomes.
Immunotherapy and Modern Agents
PD-1/PD-L1 checkpoint inhibitors (nivolumab, pembrolizumab) cause immune-related adverse events: colitis, hepatitis, and pneumonitis. Understanding these mechanisms helps you answer questions about treatment selection and management of complications.
Tumor Staging, Prognosis, and Prognostic Markers
Step 1 expects competency with TNM staging and how it influences prognosis and treatment decisions. For solid tumors, understand Tumor size (T), Node involvement (N), and Metastasis (M).
TNM Staging Fundamentals
Know that lymph node involvement generally worsens prognosis. Distant metastasis represents stage IV disease. Specific cancers have specialized staging: Hodgkin lymphoma uses the Cotswolds classification with stages I-IV and prognostic factors (A/B symptoms). Testicular cancer uses IGCCCG classification based on histology and tumor markers.
Molecular and Cellular Prognostic Markers
You must understand prognostic markers: hormone receptor status (estrogen/progesterone receptors), HER2 amplification, ki-67 proliferation index, and genetic mutations. ER/PR positive breast cancers generally have better prognosis and respond to hormone therapy. Triple-negative breast cancers have worse prognosis. Higher tumor grades indicate worse prognosis (Gleason score in prostate cancer, Bloom-Richardson in breast cancer).
Molecular Signatures and Performance Status
Recognize microsatellite instability (MSI) and mismatch repair deficiency in colorectal cancer. These indicate Lynch syndrome and predict immunotherapy response. Know that BRCA mutation carriers have increased lifetime cancer risk. Familiarize yourself with performance status (ECOG scale) as it affects treatment eligibility. Understanding these factors helps you interpret case scenarios and predict which patients are candidates for specific treatments.
Immunotherapy, Targeted Therapy, and Personalized Medicine
Modern oncology emphasizes targeted therapies based on molecular profiling, and Step 1 increasingly tests this knowledge. Understanding this shift is essential for success.
Checkpoint Inhibitors and BRAF Inhibitors
Checkpoint inhibitors (PD-1 inhibitors like nivolumab, pembrolizumab; PD-L1 inhibitors like atezolizumab) work by releasing immune brakes on T cells. They have transformed treatment of melanoma, lung cancer, and renal cell carcinoma. You must understand their mechanism, indications, and immune-related adverse events. BRAF inhibitors (vemurafenib, dabrafenib) target the V600E mutation common in melanoma. They are often combined with MEK inhibitors.
EGFR, ALK, and Tyrosine Kinase Inhibitors
EGFR inhibitors (erlotinib, gefitinib) target EGFR mutations in lung adenocarcinoma and cause characteristic rash and diarrhea. ALK inhibitors (crizotinib, alectinib) treat ALK-positive lung cancers. Know that tyrosine kinase inhibitors often cause specific toxicities: sunitinib causes hand-foot syndrome, sorafenib causes hypertension, and imatinib in CML has excellent outcomes.
HER2-Targeting and PARP Inhibitors
HER2-targeting agents (trastuzumab, pertuzumab, T-DM1) are crucial for HER2-positive breast cancers. PARP inhibitors (olaparib, rucaparib) exploit the synthetic lethality of BRCA1/BRCA2 mutations in ovarian and breast cancers. Understand that these drugs require molecular testing (tumor profiling, genetic testing) to identify candidates.
Personalized Medicine Approach
Step 1 tests your ability to match molecular abnormalities with appropriate targeted agents. Understand why personalized medicine improves outcomes. This represents the shift toward precision oncology in modern cancer care.