SACT and targeted therapy toxicities

Why does chemotherapy cause toxicity in healthy tissues?

It targets rapidly dividing cells, so high‑turnover tissues (GI tract, marrow, hair follicles) are damaged alongside cancer cells.

What are the three mechanisms behind chemotherapy‑induced diarrhoea?

Direct mucosal cell death, chronic inflammation, and microbiome imbalance.

What is the mechanism of mucositis?

Basal epithelial cell injury → ulceration → bacterial colonisation → amplified inflammatory response

Why does chemotherapy cause neutropenia?

Neutrophils have a short lifespan (~6 hours), so marrow suppression rapidly reduces counts.

What is the clinical significance of neutropenic sepsis?

It is a medical emergency requiring urgent IV antibiotics.

What causes platinum‑induced peripheral neuropathy (CIPN)?

DNA adduct formation in dorsal root ganglia, mitochondrial dysfunction, and oxidative stress

Name two patient factors increasing CIPN risk.

• Older age

• Prior neurotoxic chemotherapy

• uncontrolled diabetes

• Alcohol use

• Genetic variants (e.g., SBF2 in Black patients)

What drug can reduce anthracycline cardiotoxicity and how ?

Dexrazoxane - prevents iron overload leading to large reducing in cardiotoxicity

Why do immune checkpoint inhibitors cause toxicity?

They remove inhibitory signals on T‑cells, causing immune overactivation and autoimmune‑like inflammation.

What is the mechanism of ICI‑induced colitis?

Loss of gut immune tolerance → T‑cell infiltration → cytokine release → mucosal injury.

First‑line treatment for grade ≥2 ICI‑induced colitis?

Corticosteroids.

Why are BRAF + MEK inhibitors used together?

MEK inhibition reduces BRAF‑inhibitor‑induced skin cancers and improves efficacy