A scrape on your knee closes on its own: skin cells divide until the edges touch, and then they stop. In a tumor, by contrast, cells keep multiplying even though there is no room and no "permission" to do so. What went wrong in the internal control of those cells? At the end of the page you will come back to this question.
What cancer is
Healthy cells divide only when they receive signals that allow it, and they stop if the DNA is damaged or if there is no more space. Those decisions are made by the cell cycle checkpoints you saw in the phases of the cycle. When those controls are lost, the cell divides without restraint.
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What is cancer? Explain its relationship with cell cycle alteration.
What is cancer? Explain its relationship with cell cycle alteration.
Think of a car. To move forward in a controlled way it needs a gas pedal that responds and a brake that works. A cell has both types of control, and each one is written in genes.
A single cell usually needs several mutations, in several genes, to become cancerous. That is why cancer is more common as the years go by: there is more time for them to accumulate.
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The diagram compares the role of two types of genes in controlling cell division, in their normal form and when mutated. Explain which type of gene (proto-oncogene or…
The diagram compares the role of two types of genes in controlling cell division, in their normal form and when mutated. Explain which type of gene (proto-oncogene or tumour suppressor gene) corresponds to A and B, which kind of mutation (activating or inactivating) alters it in each case, and how each contributes to the onset of cancer.
Some mutations appear because of errors when copying DNA, but many are caused by external agents. Smoking, getting sunburned again and again, or eating corn or peanuts stored with fungi seem like very different things, and yet they share a mechanism: they damage DNA.
Some viruses promote cancer. The human papillomavirus (HPV), which is sexually transmitted, is a well-known example and the cause of almost all cervical cancers.
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Tobacco is responsible for most lung cancers. Explain what a carcinogen (or carcinogenic agent) is and give two more examples of carcinogens other than tobacco, stating…
Tobacco is responsible for most lung cancers. Explain what a carcinogen (or carcinogenic agent) is and give two more examples of carcinogens other than tobacco, stating the type of cancer they promote.
Human papillomavirus (HPV) can cause cervical cancer. Explain how a virus can induce cancerous transformation of a cell and what effective preventive measure exists…
Human papillomavirus (HPV) can cause cervical cancer. Explain how a virus can induce cancerous transformation of a cell and what effective preventive measure exists against HPV.
The cells of a tumor also need oxygen and nutrients. If the tumor is small, they reach it by diffusion from nearby vessels; if it grows a lot, the center is left without supply.
Chemotherapy
Classic chemotherapy takes advantage of the fact that tumor cells divide a lot. Many drugs act in M phase: some prevent the spindle from assembling or disassembling properly. This activates the spindle checkpoint, the cell cannot finish mitosis, and it enters programmed cell death (apoptosis).
The drug does not distinguish between a tumor cell and a healthy one: it only "sees" that the cell is dividing. That is why it damages fast-renewing healthy tissues: the bone marrow (which produces white and red blood cells, hence neutropenia and anemia), hair follicles (alopecia), and the lining of the digestive tract (lesions in the mucosa). By contrast, adult neurons and striated muscle fibers barely divide (they are in G₀), so they suffer little immediate toxicity.
The proliferation fraction is the percentage of cells in a tumor that are actively dividing. A tumor with a high fraction responds better to these drugs. A large solid tumor usually has a lower fraction: many cells are in G₀ because of a lack of oxygen or nutrients, and that is why they resist chemotherapy even though they are still alive.
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A chemotherapy drug acts by inhibiting the depolymerisation of the spindle apparatus during the M phase, which blocks the spindle assembly checkpoint and induces…
A chemotherapy drug acts by inhibiting the depolymerisation of the spindle apparatus during the M phase, which blocks the spindle assembly checkpoint and induces programmed cell death.
a) Justify at the molecular and tissue levels why this drug causes acute side effects such as neutropenia, anaemia, alopecia, and gastrointestinal mucosal lesions, whereas striated muscle tissue and nervous tissue experience almost no immediate toxicity.
b) A solid tumour has a growth fraction (percentage of cells actively dividing versus cells in G0 phase) of only 10%, while the remaining 90% is in quiescence. Predict and justify the efficacy of this chemotherapy agent against this tumour, and explain the risk posed by G0 cells re-entering the cell cycle after treatment ends.
In a preclinical trial, tumor cells are cultured to form three-dimensional multicellular spheroids in vitro. It is observed that the spheroid halts its net volumetric…
In a preclinical trial, tumor cells are cultured to form three-dimensional multicellular spheroids in vitro. It is observed that the spheroid halts its net volumetric growth upon reaching a diameter of about 1.5 mm, at which point a central core of necrotic cells appears surrounded by a peripheral rim of proliferating cells.
a) Justify at a biophysical and metabolic level why central necrosis occurs once this critical size is exceeded in the absence of a vascular network.
b) Upon implanting this spheroid into an immunocompromised mouse, the tumor induces angiogenesis and resumes rapid growth. If a neutralizing anti-VEGF monoclonal antibody is administered to the animal, predict and justify what will happen to the size of the primary tumor and to the likelihood of hematogenous metastasis formation.
Let's go back to the beginning: what went wrong in the cell that keeps dividing? It lost its brakes (suppressors) or has its gas pedal stuck (oncogenes), so it ignores the signals from the tissue. This connects with cell theory: the cell is the structural and functional unit of living things, and every cell comes from another cell. A tumor is, literally, the descendant of a single altered cell, a clone.
Seeing the cell and dividing up its functions
To study a tumor cell, the pathologist takes a biopsy, cuts it into very thin slices, stains it, and observes it under the light microscope. The dyes highlight structures: the nucleus stains intensely and lets you see its size and shape. With the electron microscope, smaller organelles can be distinguished, such as mitochondria. The total magnification is that of the eyepiece multiplied by that of the objective; for example, eyepiece ×10 and objective ×40 give ×400.
Each organelle performs a different function, and that makes it possible to interpret what is seen. The nucleus holds the DNA and directs the cell cycle; in cancer cells it is usually large, irregular, and heavily stained. Mitochondria produce most of the ATP that sustains rapid division. Ribosomes make proteins, including those that regulate the cycle. The mitotic spindle, formed by microtubules of the cytoskeleton, distributes the chromosomes in mitosis, and it is the target of several chemotherapy drugs. If an organelle fails, its function fails; that is why the appearance of the cell tells you about its state.
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Analyze the following two clinical cases seen in an oncology unit: Patient A: A 65-year-old smoker diagnosed with lung squamous cell carcinoma. Genomic analysis reveals…
Analyze the following two clinical cases seen in an oncology unit:
Patient A: A 65-year-old smoker diagnosed with lung squamous cell carcinoma. Genomic analysis reveals inactivating mutations in the TP53 gene exclusively in cells from the tumor biopsy, but not in his blood lymphocytes or his sperm.
Patient B: A 32-year-old woman diagnosed with bilateral breast cancer. Genetic testing detects a pathogenic mutation in the BRCA1 gene in all her somatic cells and in her oocytes, an alteration also present in her mother and maternal grandmother.
a) Based on these data, refute the apparent contradiction in the statement "cancer is always a genetic disease, but rarely hereditary," by assigning and justifying for each patient the type of mutation (somatic or germline) and its impact on offspring.
b) Applying Knudson's two-hit hypothesis for tumor suppressor genes, explain why Patient B developed the tumor at such an early age, and clarify why inheriting this germline mutation does not mean being born with an already developed tumor.