High-yield map
Key points before the detail
- 01
Drivers contribute to tumour fitness; passengers are carried along without materially driving the cancer phenotype.
- 02
Oncogene activation is typically gain-of-function at the cellular level; tumour-suppressor pathways usually require functional loss.
- 03
Tumour heterogeneity develops through clonal evolution and affects treatment resistance.
- 04
Metastasis requires invasion, intravasation, survival, extravasation and colonisation; completing the final colonisation step is biologically difficult.
Carcinogenesis is a multistep evolutionary process
Inherited susceptibility, environmental exposures, chronic injury and replication errors can all contribute mutations or epigenetic changes. Clones that acquire a survival or proliferative advantage expand, creating opportunities for additional alterations. The older initiation–promotion–progression model remains useful conceptually, but human cancers do not all follow one identical sequence.
Oncogenes and tumour suppressors
| Class | What goes wrong | Examples |
|---|---|---|
| Proto-oncogene → oncogene | Gain or overactivity of growth/survival signalling | RAS, MYC, ERBB2/HER2 |
| Tumour-suppressor pathway | Loss of growth restraint, genome surveillance or cell-cycle control | TP53, RB1, APC |
| DNA-repair genes | Defective repair increases the rate at which additional mutations accumulate | Mismatch-repair and homologous-recombination pathways in relevant cancers |
Clonal evolution creates heterogeneity
A tumour is not genetically and phenotypically uniform. Subclones compete under changing conditions such as hypoxia, immune pressure and treatment. A resistant clone may be minor before therapy and dominant afterwards. This is why one biopsy can incompletely represent a large or metastatic cancer.
Local invasion
Invasion requires changes in cell adhesion, interaction with extracellular matrix, motility and protease systems. Reduced epithelial cohesion, including altered E-cadherin function in selected cancers, can facilitate detachment. Tumour and stromal cells remodel basement membrane and interstitial matrix, allowing malignant cells to migrate through tissue planes.
The metastatic cascade
| Step | Biological challenge |
|---|---|
| Local invasion | Escape the primary epithelial/tissue compartment. |
| Intravasation | Enter lymphatic or blood vessels. |
| Circulatory survival | Resist shear stress, immune attack and anoikis; platelet interactions can help selected tumour cells. |
| Arrest and extravasation | Adhere and cross endothelium at a distant site. |
| Colonisation | Adapt to and grow within a foreign tissue microenvironment. |
Active recall
Close the notes and answer these
Try each question from memory before revealing the answer. These public prompts are a small preview of the integrated retrieval system inside SurgAtlas.
01What is the difference between a driver and passenger alteration?
A driver confers a selective advantage or contributes to malignant behaviour; a passenger is present in the clone without materially driving that phenotype.
02How do oncogenes and tumour suppressors differ conceptually?
Oncogenes result from gain/overactivity of growth-promoting functions, whereas tumour-suppressor pathways lose restraining functions.
03List the major stages of the metastatic cascade.
Local invasion, intravasation, survival in transit, arrest/extravasation and successful colonisation at the distant site.
Sources & editorial basis
References & editorial basis
- SurgAtlas production chapter — Carcinogenesis and Oncogenes. Primary source for this public lesson. The public teaching is a condensed, source-derived version of the corresponding production pathology chapter.
- Robbins & Cotran Pathologic Basis of Disease. Reference for stable molecular and metastatic principles.
This lesson is derived from the corresponding SurgAtlas production teaching material. Where the source makes current management or guideline claims, the public lesson uses the cited contemporary guidance. It is written for education and examination preparation, not as patient-specific clinical advice.
Editorial details
Medical Doctor (MD) · MRCS Part A · Physician · Surgical Educator
SurgAtlas is an educational resource. For patient care, verify current national guidance, local antimicrobial and transfusion policies, specialty pathways and individual patient factors.
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