Cancer Medical Glossary

Treatment given after the primary treatment (usually surgery) to reduce the risk of cancer coming back. The word 'adjuvant' means 'helping' — it helps the main treatment do a better job. Common examples: chemotherapy after colon cancer surgery, radiation after breast-conserving surgery, hormone therapy after hormone-receptor-positive breast cancer surgery.

The most common type of cancer, arising from gland-forming cells (cells that normally produce secretions like mucus). Most colorectal, lung, breast, pancreatic, and prostate cancers are adenocarcinomas. The name comes from 'adeno' (gland) + 'carcinoma' (cancer of epithelial tissue).

A class of chemotherapy drugs that work by attaching an alkyl group to DNA, causing cross-links that prevent cancer cells from replicating. They were among the first chemotherapy drugs — derived from mustard gas research. Examples: cyclophosphamide, temozolomide (for glioblastoma), carboplatin, cisplatin.

AMP-activated protein kinase — the cell's master energy sensor. When energy is low (during fasting, caloric restriction, or exercise), AMPK is activated. It switches cells to energy conservation mode: it inhibits mTOR (a growth promoter), stimulates autophagy (cellular cleanup), and improves insulin sensitivity. Metformin activates AMPK, which is one reason it has anti-cancer interest.

The formation of new blood vessels. Tumours need a blood supply to grow beyond a few millimetres — they hijack angiogenesis by secreting VEGF (vascular endothelial growth factor) to grow their own vasculature. Anti-angiogenic drugs (bevacizumab/Avastin, sunitinib) and anti-angiogenic foods (green tea, resveratrol, berries) target this process.

Programmed cell death — the cell's built-in self-destruct mechanism. Normal cells that accumulate too many DNA errors or receive the wrong signals trigger apoptosis and die cleanly without causing inflammation. One hallmark of cancer is evading apoptosis: cancer cells disable or bypass these death signals. Many anti-cancer drugs work by forcing cancer cells back into apoptosis.

The cell's self-cleaning process — 'auto' (self) + 'phagy' (eating). Cells package damaged proteins and organelles into vesicles, digest them, and recycle the components. Fasting, caloric restriction, and certain compounds (resveratrol, spermidine) trigger autophagy. Its role in cancer is complex: autophagy can suppress early tumour formation but can also help established tumours survive stress.

A protein normally produced by the fetal liver and yolk sac, declining to very low levels after birth (normal <10 ng/mL in adults). AFP is markedly elevated in hepatocellular carcinoma (HCC/liver cancer) and non-seminomatous germ cell tumours (testicular cancer). It is used in diagnosis, staging, treatment monitoring, and surveillance after treatment. AFP combined with ultrasound is the standard screening tool for HCC in cirrhotic patients.

The number of neutrophils (the primary white blood cells that fight bacterial infections) per microlitre of blood. Calculated as: total WBC × (% neutrophils + % bands) ÷ 100. Normal ANC: 1.8–7.7 × 10⁹/L. Neutropenia is classified by severity: mild (1.0–1.8), moderate (0.5–1.0), severe (<0.5), and profound (<0.1). Febrile neutropenia — fever (≥38.3°C) plus ANC <0.5 — is an oncological emergency.

A chromosomal rearrangement (most commonly EML4-ALK fusion) found in approximately 3–5% of non-small cell lung cancers (NSCLC), typically in younger, never/light smokers with adenocarcinoma histology. Detected by FISH, IHC, or NGS. ALK-rearranged lung cancers are highly sensitive to ALK tyrosine kinase inhibitors: crizotinib (1st gen), alectinib, brigatinib (2nd gen), lorlatinib (3rd gen — active against brain metastases).

Chemotherapy drugs that mimic the building blocks of DNA or RNA (nucleotides) and interfere with their synthesis or incorporation, blocking DNA replication and cell division. Classes include: fluoropyrimidines (5-fluorouracil/5-FU, capecitabine — inhibit thymidylate synthase), folate antagonists (methotrexate, pemetrexed — inhibit DHFR and TYMS), purine analogues (gemcitabine, fludarabine, cladribine). Most active against rapidly dividing cells.

Polysaccharides (complex sugars) found in the cell walls of mushrooms, oats, and yeast. They bind to receptors on macrophages and natural killer (NK) cells, activating the innate immune system. Mushroom-derived beta-glucans — particularly PSK (from turkey tail) and lentinan (from shiitake) — have been approved as adjunct cancer therapies in Japan since the 1980s.

A measurable biological indicator — something in blood, tissue, or imaging that tells you something meaningful about a disease or treatment response. Biomarkers can be genetic (BRCA1 mutation), protein-based (HER2 overexpression, PSA level), or imaging-based (tumour size on CT). They guide treatment decisions: a HER2+ biomarker means a patient benefits from trastuzumab (Herceptin).

A monoclonal antibody that blocks VEGF (vascular endothelial growth factor), starving tumours of their blood supply. FDA approved for colorectal, lung, ovarian, cervical, glioblastoma, and other cancers. Given IV every 2–3 weeks. It is the most successful anti-angiogenic drug to date.

BReast CAncer genes 1 and 2 — tumour suppressor genes responsible for repairing double-strand DNA breaks via homologous recombination. When mutated, DNA repair is defective, and cells accumulate mutations. BRCA1/2 mutations cause hereditary breast and ovarian cancer syndrome. People with BRCA mutations have 50–85% lifetime breast cancer risk and 15–45% ovarian cancer risk. They also confer elevated risk for pancreatic, prostate, and male breast cancer.

The removal of a tissue sample from the body for examination under a microscope by a pathologist to determine whether cancer cells are present and, if so, what type. Types include core needle biopsy (a hollow needle removes a cylinder of tissue), fine needle aspiration (FNA — thin needle, cell clusters only), excisional biopsy (surgical removal of the whole lesion), and punch biopsy (skin). The pathology report from a biopsy is the definitive cancer diagnosis — nothing else can confirm cancer.

Next-generation trial designs that match treatments to tumour molecular profiles rather than tumour location. Basket trials enrol patients with the same biomarker (e.g., NTRK fusion) across multiple cancer types — all treated with the same targeted drug (e.g., larotrectinib). Umbrella trials screen many patients with one cancer type, assigning them to different targeted therapies based on individual tumour profiling. Master protocols like NCI-MATCH, TAPUR, and MyPathway use these adaptive designs to test multiple drugs simultaneously.

Chimeric Antigen Receptor T-cell therapy. Patient's T cells are collected from blood, genetically engineered in the lab to express artificial receptors (CARs) that recognise a specific cancer protein, multiplied into millions of cells, then reinfused. The engineered T cells then seek and destroy cancer cells displaying that protein. Currently approved for blood cancers (ALL, DLBCL, multiple myeloma). Solid tumour CAR-T is under active research.

Cancer arising from epithelial cells — the cells that line organs and body surfaces (skin, gut, lung, breast, prostate). Carcinomas account for about 90% of all human cancers. Subtypes include adenocarcinoma (gland-forming cells), squamous cell carcinoma (flat cells), and transitional cell carcinoma (bladder lining).

A class of immunotherapy drugs that block the 'off switches' (immune checkpoints) that cancer cells use to hide from the immune system. The main targets: PD-1 (pembrolizumab/Keytruda, nivolumab/Opdivo), PD-L1 (atezolizumab, durvalumab), and CTLA-4 (ipilimumab/Yervoy). By blocking these brakes, T cells remain active and can kill cancer cells.

Cytotoxic T-Lymphocyte-Associated protein 4 — an immune checkpoint receptor on T cells that sends an inhibitory signal, dampening the immune response. It competes with CD28 (an activating receptor) for binding to B7 ligands on antigen-presenting cells. Cancer cells exploit CTLA-4 signalling to prevent T-cell activation. Ipilimumab (Yervoy) blocks CTLA-4, releasing the brake on T-cell activation.

The TNM system describes cancer extent: T = tumour size/invasion (T1–T4), N = lymph node involvement (N0–N3), M = distant metastasis (M0 = none, M1 = present). Combined into stages I–IV. Stage I = localised, small, no node involvement. Stage IV = distant metastasis. Staging determines treatment options, clinical trial eligibility, and prognosis.

Cancer Antigen 125 — a glycoprotein shed into the bloodstream by ovarian surface epithelial cells, particularly when ovarian cancer is present. Blood levels are measured in units/mL; values above 35 U/mL are generally considered elevated. CA-125 is primarily used to monitor ovarian cancer treatment response and detect recurrence, not as a population screening tool (it lacks specificity, rising in endometriosis, fibroids, and other conditions).

A glycoprotein normally produced during fetal development that returns to low levels after birth (normal <3 ng/mL in non-smokers, <5 in smokers). CEA is elevated in colorectal, lung, breast, pancreatic, gastric, and thyroid cancers. It is not specific enough for cancer screening, but it is widely used to monitor treatment response and detect recurrence in colorectal cancer. Baseline CEA before surgery and serial monitoring post-operatively is standard care for colorectal cancer.

A protein produced by the liver in response to inflammation. CRP rises within hours of inflammatory stimulus, making it a sensitive but non-specific marker. In oncology, elevated CRP is associated with tumour-promoting inflammation, cachexia (cancer wasting), and is an independent negative prognostic factor in many cancers including lung, colorectal, ovarian, and lymphoma. High-sensitivity CRP (hsCRP) measures very low levels relevant to chronic inflammation.

A standard blood panel measuring the three main cell types: red blood cells (RBCs, haemoglobin, haematocrit), white blood cells (WBCs — total and differential count including neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelets. CBC is run before every chemotherapy cycle to check whether the patient's bone marrow is recovering adequately. Key values: haemoglobin (anaemia), WBC differential (infection risk), platelets (bleeding risk).

Fragments of DNA shed by cancer cells into the bloodstream, detectable in a blood draw. ctDNA carries the same mutations as the tumour, allowing tumour-specific changes to be tracked non-invasively. ctDNA assays (Guardant360, FoundationOne Liquid CDx, Signatera) can detect mutations, copy number alterations, and fusions. Sensitivity is proportional to tumour burden — more advanced disease sheds more ctDNA.

Intact cancer cells that have detached from the primary tumour or metastases and entered the bloodstream. CTCs are extremely rare (often just 1–10 per 7.5 mL of blood among billions of normal blood cells). The CellSearch system is the only FDA-cleared CTC test, used for monitoring in metastatic breast, colorectal, and prostate cancer. High CTC counts predict worse prognosis and earlier disease progression.

Carbohydrate Antigen 19-9 — a glycoprotein elevated in pancreatic cancer (sensitivity ~80%), biliary tract cancer, and to a lesser degree in gastric and colorectal cancers. Normal value: <37 U/mL. CA 19-9 cannot be used alone for diagnosis (it is not specific), but is the most useful serum marker for pancreatic cancer monitoring. Note: approximately 5–10% of individuals who are Lewis antigen-negative cannot produce CA 19-9 — these patients will always have falsely low levels.

A complex metabolic syndrome characterised by unintentional weight loss (>5% body weight), muscle wasting (sarcopenia), fatigue, and loss of appetite, caused by tumour-secreted inflammatory cytokines (TNF-α, IL-6, IL-1) and metabolic reprogramming. Cachexia is NOT simply malnutrition — it cannot be fully reversed by eating more, because it is driven by active catabolism at the cellular level. Affects 50–80% of advanced cancer patients and accounts for ~20% of cancer deaths.

A minimally invasive procedure that destroys tumour cells by freezing them to extreme temperatures (−40°C to −170°C) using argon gas circulated through thin needles inserted directly into the tumour under imaging guidance (CT or ultrasound). The ice crystal formation and osmotic stress rupture cancer cell membranes. Repeated freeze-thaw cycles maximise cell death. Used for kidney tumours, liver metastases, lung nodules, prostate cancer, breast tumours, and bone metastases for pain relief.

Drugs that block cyclin-dependent kinases 4 and 6 — enzymes that control cell cycle progression from the G1 phase to S phase (DNA replication). Approved agents: palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Verzenio). Combined with aromatase inhibitors or fulvestrant for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer as first- or second-line therapy. Abemaciclib is also approved in the adjuvant setting for high-risk early HR+ breast cancer.

A regulatory pathway allowing patients with serious conditions to access investigational drugs, biologics, or medical devices outside of a clinical trial — typically when no comparable alternative therapy is available. In the US, managed by the FDA's Expanded Access Programme; in the EU, by individual member state compassionate use programmes; in Australia by the TGA's Special Access Scheme. May be individual patient access, intermediate-size access, or widespread expanded access protocols.

The 'generals' of the immune system — professional antigen-presenting cells that bridge innate and adaptive immunity. They patrol tissues, engulf pathogens and cancer cells, process their proteins into fragments (antigens), and present these fragments to T cells in lymph nodes, activating a targeted immune response. Dendritic cell vaccines (like DCVax-L, Provenge) use the patient's own dendritic cells, loaded with tumour antigens ex vivo, to prime anti-tumour T cells.

The cellular machinery that detects and repairs DNA damage. Key players include BRCA1/2 (homologous recombination), ATM, ATR, PARP (base excision repair), and TP53. When DDR genes are mutated, DNA errors accumulate — eventually leading to cancer. However, DDR-deficient cancers are also often more sensitive to DNA-damaging chemotherapy and PARP inhibitors.

Epidermal Growth Factor Receptor — a protein on the cell surface that, when activated by growth factors, signals cells to grow and divide. EGFR mutations (exon 19 deletions, exon 21 L858R) are found in 10–15% of NSCLC in Western patients and up to 50% in East Asian patients. EGFR-mutated lung cancer responds dramatically to EGFR tyrosine kinase inhibitors (TKIs): osimertinib, erlotinib, gefitinib.

Changes to gene expression that don't alter the DNA sequence itself — but change whether genes are switched on or off. Mechanisms include DNA methylation (adding methyl groups to silence genes) and histone modification (changing how DNA is packaged). Cancer often involves silencing tumour suppressor genes via aberrant methylation or activating oncogenes through demethylation. Lifestyle factors (diet, stress, toxins) can influence epigenetics.

A hierarchy ranking how reliable a piece of scientific evidence is. From strongest to weakest: (1) Systematic reviews & meta-analyses of RCTs, (2) Randomised Controlled Trials (RCTs), (3) Cohort studies, (4) Case-control studies, (5) Case reports, (6) Expert opinion. On this site, 'strong' evidence = RCTs; 'moderate' = multiple cohort studies or Phase 2 trials; 'preliminary' = early Phase 1 or lab studies.

First-line therapy is the initial treatment given for a cancer. If it stops working (disease progresses) or causes intolerable side effects, patients move to second-line, then third-line therapy. Each subsequent line typically has lower response rates. 'Front-line' and 'first-line' mean the same thing.

A standard chemotherapy regimen for colorectal cancer: FOLinic acid (leucovorin) + Fluorouracil (5-FU) + OXaliplatin. Given IV every 2 weeks. FOLFOX4 and mFOLFOX6 are common variants. Often combined with bevacizumab (FOLFOX + bev) or cetuximab (for RAS wild-type tumours).

A germline mutation is inherited — it is present in every cell of the body from birth (including egg and sperm cells), meaning it can be passed to children. Example: BRCA1/2 germline mutations cause hereditary breast/ovarian cancer. A somatic mutation occurs during a person's lifetime, only in specific cells (like a tumour), and cannot be inherited. Most cancer mutations are somatic.

The 10 capabilities that cancer cells must acquire to become malignant, described by Hanahan & Weinberg (2000, updated 2011 and 2022): (1) sustaining proliferative signalling, (2) evading growth suppressors, (3) resisting cell death (apoptosis), (4) enabling replicative immortality, (5) inducing angiogenesis, (6) activating invasion & metastasis, (7) reprogramming energy metabolism (Warburg effect), (8) evading immune destruction, (9) tumour-promoting inflammation, (10) genome instability.

Human Epidermal growth factor Receptor 2 — a protein on the surface of cells that promotes growth. In 15–20% of breast cancers and 10–15% of gastric cancers, the HER2 gene is amplified (extra copies), leading to HER2 overexpression, which drives aggressive tumour growth. Tested by IHC (immunohistochemistry: 0, 1+, 2+, 3+) and FISH. HER2+ cancers respond to trastuzumab (Herceptin), pertuzumab, T-DM1, T-DXd (Enhertu).

A state where cancer cells cannot repair double-strand DNA breaks via homologous recombination — the high-fidelity repair pathway. HRD is caused by BRCA1/2 mutations and other gene mutations (RAD51, PALB2, ATM). HRD-positive tumours rely on alternative, error-prone repair pathways (NHEJ, PARP-mediated base excision repair), making them uniquely vulnerable to PARP inhibitors.

The microscopic examination of tissue to study cell structure and identify disease. In oncology, histopathology of a biopsy specimen determines: cancer type (carcinoma, sarcoma, lymphoma), subtype (adenocarcinoma, squamous cell), grade (how abnormal cells look), and special features (lymphovascular invasion, perineural invasion, margin status). Immunohistochemistry (IHC) adds protein staining to identify biomarkers (ER, PR, HER2, PD-L1, MMR proteins).

A surgical procedure combining cytoreductive surgery (CRS) — removing all visible tumour from the abdominal cavity — with heated chemotherapy (typically cisplatin or mitomycin C, warmed to 41–43°C) circulated directly inside the abdomen for 30–90 minutes before closing. The heat enhances drug penetration into tissues and has independent anti-tumour effects. Used for peritoneal metastases from colorectal cancer, ovarian cancer, appendiceal cancer (pseudomyxoma peritonei), and mesothelioma.

Treatment that blocks or lowers hormone levels to slow the growth of hormone-sensitive cancers. In breast cancer: tamoxifen (SERM — blocks oestrogen receptors), aromatase inhibitors (letrozole, anastrozole, exemestane — block oestrogen production in post-menopausal women), and CDK4/6 inhibitors are added for metastatic HR+ disease. In prostate cancer: androgen deprivation therapy (ADT — GnRH agonists/antagonists: leuprolide, degarelix) suppresses testosterone; enzalutamide and abiraterone block androgen signalling even at low testosterone levels.

A treatment modality that raises tumour temperature to 39–45°C using microwave, radiofrequency, or ultrasound energy, enhancing the effect of radiotherapy and chemotherapy. At hyperthermic temperatures, cancer cells (which have impaired heat-shock responses compared to normal cells) suffer membrane damage and protein denaturation. Hyperthermia sensitises tumour cells to radiation (particularly in hypoxic tumour regions that are radiation-resistant) and platinum-based chemotherapy. HIPEC (heated intraperitoneal chemo) is one application.

Intravenous vitamin C (IVC) at pharmacological doses (25–100 g/infusion) achieves plasma concentrations 100–500× higher than oral supplementation can reach. At these concentrations, ascorbate acts as a pro-oxidant in the tumour microenvironment — generating hydrogen peroxide selectively in cancer tissue (which has poor catalase activity), while acting as an antioxidant in normal tissues. IVC is being tested in combination with chemotherapy (gemcitabine, FOLFOX) and radiation in Phase 1/2 trials.

Side effects caused by immunotherapy (especially checkpoint inhibitors) where the unleashed immune system attacks normal tissues. Can affect any organ: pneumonitis (lungs), colitis (gut), hepatitis (liver), thyroiditis/hypophysitis (endocrine), myocarditis (heart — rare but serious), nephritis (kidneys), rash. Usually managed with corticosteroids. Can occur months after stopping treatment.

Deliberate periods of caloric restriction or complete fasting (ranging from 12–16 hour overnight fasts to multi-day water-only fasts or fasting-mimicking diets). In the cancer context, fasting is proposed to: (1) lower insulin and IGF-1 (growth signals exploited by cancer), (2) activate AMPK and suppress mTOR (anti-proliferative), (3) induce autophagy (cellular cleanup), (4) protect normal cells from chemotherapy toxicity while leaving cancer cells vulnerable ('differential stress sensitisation'), and (5) potentially enhance immunotherapy efficacy.

KRAS (Kirsten RAS) is a proto-oncogene encoding a GTPase protein that acts as an on/off switch for cell growth signals. KRAS mutations (most commonly G12D, G12V, G12C) lock it permanently 'on,' driving uncontrolled proliferation. KRAS is mutated in ~40% of colorectal, ~25% of lung, and ~90% of pancreatic cancers. Historically considered 'undruggable' — but KRAS G12C-specific inhibitors (sotorasib, adagrasib) were approved in 2021–2022.

A nuclear protein expressed only in actively proliferating cells — it is absent in resting (G0) cells. Ki-67 is measured by immunohistochemistry (IHC) on tumour biopsy tissue and expressed as a percentage of cells staining positive. It is a direct measure of tumour proliferation rate. In breast cancer, Ki-67 <14–20% is low (less aggressive), 20–30% intermediate, and >30% high (aggressive). Ki-67 is also used in neuroendocrine tumours to define grade.

A very high-fat (70–80% of calories), very low-carbohydrate (<20–50 g/day), adequate-protein diet that shifts the body from glucose-based to fat-based metabolism, generating ketone bodies (beta-hydroxybutyrate, acetoacetate) as the primary fuel. Cancer cells, which preferentially ferment glucose (Warburg effect), may be unable to utilise ketones efficiently, creating metabolic stress. Therapeutic application in cancer is championed by researchers including Thomas Seyfried and Valter Longo.

A blood test that detects cancer-derived material circulating in the bloodstream — primarily circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs). Unlike surgical biopsy, it is minimally invasive, can be repeated serially, and captures the full tumour heterogeneity (including multiple tumour sites). Used for treatment monitoring, early detection of recurrence, and identifying resistance mutations.

The most common hereditary colorectal cancer syndrome, caused by germline mutations in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2. Causes high lifetime risk of colorectal (50–80%), endometrial (25–60%), ovarian, gastric, and other cancers. Importantly, Lynch syndrome tumours are MSI-H (microsatellite instability-high) and respond exceptionally well to checkpoint inhibitors (pembrolizumab). Identified via IHC on tumour tissue or germline genetic testing.

An enzyme found in nearly all body cells that converts pyruvate to lactate during anaerobic metabolism. Elevated serum LDH indicates rapid cell turnover, cell death, or tissue damage. In oncology, high LDH is a non-specific but important prognostic marker in lymphoma (part of the International Prognostic Index), melanoma, testicular cancer, and small cell lung cancer. Normal range: typically 140–280 U/L (varies by lab).

Both are blood cancers but arise differently. Lymphoma is cancer of lymphocytes that forms solid masses in lymph nodes, spleen, or other organs — divided into Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL, 60+ subtypes including DLBCL, follicular, mantle cell, Burkitt). Leukaemia is cancer of blood-forming cells in the bone marrow that overproduces abnormal blood cells — divided by acuity (acute vs chronic) and lineage (myeloid vs lymphoid): AML, ALL, CML, CLL.

Naltrexone is an opioid receptor antagonist approved at 50 mg for alcohol and opioid dependence. At low doses (1.5–4.5 mg, typically taken at night), it transiently blocks opioid receptors for a few hours, causing a rebound increase in endorphin and enkephalin production. This rebound is proposed to enhance immune function — particularly NK cell activity and Th1 cytokine production — and reduce pathological inflammation. LDN is not FDA-approved for cancer, but is used off-label and being investigated in several cancer types.

The spread of cancer from its original site to other parts of the body through the bloodstream or lymphatic system. The new tumours are called metastases (or 'mets'). Metastatic cancer retains the characteristics of its origin — breast cancer that has spread to the liver is still breast cancer (not liver cancer) and is treated with breast cancer drugs.

O-6-Methylguanine-DNA Methyltransferase — a DNA repair enzyme that reverses alkylation damage to DNA. When the MGMT gene's promoter region is methylated (silenced by epigenetics), cancer cells cannot repair DNA damage caused by alkylating agents (like temozolomide). This makes MGMT-methylated glioblastomas (GBM) much more sensitive to temozolomide chemotherapy.

Antibodies engineered to target a single, specific protein (antigen). In cancer, they target proteins on cancer cells (HER2, VEGF, CD20, EGFR, PD-1, PD-L1). Names ending in '-mab' (trastuzumab, bevacizumab, pembrolizumab, cetuximab). They work by blocking signalling receptors, marking cancer cells for immune destruction, or delivering a payload (antibody-drug conjugates).

Microsatellite Instability-High (MSI-H) and deficient Mismatch Repair (dMMR) are two ways of describing the same tumour characteristic — defective DNA mismatch repair leading to thousands of mutations. MSI-H tumours have very high tumour mutational burden (TMB-H) and are typically highly immunogenic (easily recognised by the immune system). Pembrolizumab is approved for any MSI-H/dMMR solid tumour regardless of cancer type — the first ever tumour-agnostic approval.

Mechanistic Target of Rapamycin — a master regulator of cell growth, proliferation, and metabolism. When mTOR is active, cells grow; when it is inhibited, cells slow down or activate autophagy. Cancer cells frequently have hyperactive mTOR (driven by PI3K/AKT pathway mutations). mTOR inhibitors (everolimus, temsirolimus) are approved for breast, kidney, and neuroendocrine cancers. Fasting and caloric restriction potently suppress mTOR.

Drugs that block mTOR (mechanistic target of rapamycin), a key regulator of cell growth and metabolism. Rapalogs (rapamycin analogues): everolimus (Afinitor) and temsirolimus (Torisel) — approved for hormone receptor-positive metastatic breast cancer (with exemestane), renal cell carcinoma, neuroendocrine tumours (pancreatic and GI), and TSC-related tumours. They block mTORC1, causing G1 cell cycle arrest. Hyperglycaemia, immunosuppression, non-infectious pneumonitis, and mucositis are class side effects.

See also the Monoclonal Antibody (mAb) entry in this glossary. As a drug class, therapeutic mAbs are grouped by mechanism: naked mAbs (trastuzumab, bevacizumab, cetuximab, rituximab), checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab), bispecific antibodies (blinatumomab — simultaneously binds cancer cells and T cells), and antibody-drug conjugates (ADCs — mAb linked to a cytotoxic payload; e.g., T-DM1, T-DXd, sacituzumab govitecan). All end in '-mab'.

Extracts of European mistletoe (Viscum album) containing lectins (ML-I, ML-II, ML-III) and viscotoxins — proteins with direct cytotoxic and immune-modulating effects. Mistletoe injections (subcutaneous or IV) are among the most widely used complementary cancer therapies in Europe, particularly Germany and Switzerland. They are proposed to stimulate NK cells and T cells, induce apoptosis in cancer cells, improve quality of life (fatigue, nausea), and reduce immunosuppression. Marketed as Iscador, Helixor, and Abnoba Viscum.

Administration of low-dose chemotherapy on a frequent or continuous schedule (daily or multiple times per week) rather than the conventional high-dose, intermittent approach. Metronomic dosing targets the tumour's blood supply (anti-angiogenic via VEGF suppression), stimulates regulatory T-cell depletion (immunomodulatory), and may overcome drug resistance at sub-toxic doses. Common metronomic agents: cyclophosphamide, methotrexate, capecitabine, vinorelbine.

An integrative approach to cancer treatment that targets the metabolic abnormalities of cancer cells rather than their genetic mutations. Based primarily on the work of Professor Thomas Seyfried (Boston College), it views cancer as primarily a mitochondrial metabolic disease driven by the Warburg effect. Core elements of Seyfried's 'Press-Pulse' protocol: ketogenic/restricted diet (press) combined with metabolic drugs — typically a combination including the GKI (glucose-ketone index) target, and adjuncts like metformin, hyperbaric oxygen therapy, and 2-deoxy-D-glucose.

A mutant protein fragment created by tumour-specific mutations that is presented on the cancer cell surface via MHC molecules. Unlike normal self-antigens (which the immune system is trained to ignore) or tumour-associated antigens (which are overexpressed normal proteins), neoantigens are truly foreign — the immune system has never seen them before. Personalised cancer vaccines (mRNA-4157, BNT122) encode neoantigens to train the immune system to find and kill cells carrying them.

Treatment given before the primary treatment (usually surgery) to shrink the tumour, making surgery easier or less extensive. Common examples: chemotherapy before breast cancer surgery (to allow breast-conserving surgery), chemoradiation before rectal cancer surgery (to downstage the tumour), immunotherapy before lung cancer resection.

High-throughput DNA sequencing technology that can rapidly sequence millions of DNA fragments in parallel. In oncology, NGS is used to analyse hundreds to thousands of cancer-relevant genes simultaneously from a tumour sample (comprehensive genomic profiling). Platforms: Foundation One CDx, Tempus xT, Caris MI Profile, MSK-IMPACT. Identifies mutations, fusions, copy number alterations, MSI status, and TMB.

Innate immune cells that can kill cancer cells and virus-infected cells without prior sensitisation — they don't need to be 'taught' what to look for first. NK cells recognise cells that have lost MHC-I expression (a common cancer escape mechanism) and kill them via perforin and granzyme release. NK cell activity is enhanced by beta-glucans (mushrooms), IL-2, and is suppressed by stress, poor sleep, and alcohol.

Overall survival (OS) is the gold standard endpoint: how long patients live from a defined starting point. Progression-free survival (PFS) measures how long patients live without their disease getting worse. PFS improves faster in trials (shorter follow-up needed) but doesn't always translate to OS benefit. Other endpoints: objective response rate (ORR) — percentage of patients whose tumour shrinks; pathological complete response (pCR) — no cancer in surgical specimen; duration of response (DOR).

A clinical trial in which both the participants and the investigators know which treatment is being administered. This contrasts with blinded trials (single-blind: only the patient is unaware; double-blind: both patient and investigator are unaware). Open-label trials are common in cancer research because: ethical concerns prevent using a placebo instead of an active treatment, cancer treatments are often too toxic or visually distinct to blind, and objective endpoints (tumour shrinkage on scans) are less susceptible to placebo effects than subjective endpoints.

Palliative care focuses on relieving symptoms and improving quality of life rather than curing the disease. 'Palliative intent' treatment aims to control cancer and extend life, but not to cure it. Importantly, palliative care is not the same as end-of-life or hospice care — it can and should begin at diagnosis alongside curative treatments. Studies show palliative care improves survival and quality of life when started early.

Poly ADP-ribose polymerase inhibitors — drugs that block an alternative DNA repair pathway (base excision repair) that cancer cells with BRCA/HRD mutations rely on when their primary repair (homologous recombination) is broken. This concept is called 'synthetic lethality': each defect alone is survivable, but both together kill the cell. Approved PARP inhibitors: olaparib (Lynparza), niraparib (Zejula), rucaparib (Rubraca), talazoparib (Talzenna).

PD-1 (Programmed Death-1) is a receptor on T cells that, when bound by PD-L1 (its ligand expressed on cancer cells and normal cells), sends an inhibitory signal that 'exhausts' the T cell — preventing it from killing. This is a normal mechanism to prevent autoimmunity, but cancer cells exploit it to hide from immunity. Anti-PD-1 drugs (pembrolizumab, nivolumab) block this interaction, reactivating T cells against cancer.

Phase 1: First-in-human testing — primarily assesses safety, dosing, and side effects. Small cohorts (15–50 patients), often without a control group. Phase 2: Tests whether the treatment works in a larger group (50–300 patients), assesses efficacy and further safety. May be single-arm (no comparison group) or randomised. Phase 3: Large randomised controlled trial (300–3000+ patients) comparing new treatment to standard of care. This is the definitive evidence for approval.

A protein produced by both normal and malignant prostate cells, measured in nanograms per millilitre (ng/mL). PSA is used for prostate cancer screening, diagnosis, and monitoring. Elevated PSA can be caused by prostate cancer, benign prostatic hyperplasia (BPH), prostatitis, or recent ejaculation. PSA density (PSA ÷ prostate volume) and PSA velocity (rate of rise) improve specificity. Values above 4 ng/mL traditionally trigger biopsy consideration, though many centres now use 3 ng/mL.

Programmed Death-Ligand 1 — a protein expressed on tumour cells and immune cells within the tumour microenvironment. Measured by immunohistochemistry (IHC) as a percentage, using the Tumour Proportion Score (TPS) or Combined Positive Score (CPS). Different assays (22C3, 28-8, SP142, SP263) are paired with specific checkpoint inhibitors. High PD-L1 expression (TPS ≥50% in NSCLC) strongly predicts pembrolizumab response without chemotherapy.

The primary tumour is the cancer at the site where it originally arose — for example, a primary lung cancer that starts in lung cells. A secondary tumour (also called a metastasis or 'met') is a colony of cancer cells that has spread from the primary site to a different location — for example, lung cancer that has spread to the liver. The secondary tumour is still lung cancer, not liver cancer, and retains the biology of its origin.

A group of rare disorders caused not by direct tumour invasion but by tumour-secreted substances (hormones, antibodies, cytokines) that act on distant organs. Examples: Cushing's syndrome from ACTH secreted by small cell lung cancer, hypercalcaemia from PTHrP secreted by squamous cell carcinomas, Lambert-Eaton myasthenic syndrome (neuromuscular weakness) from antibodies triggered by SCLC, inappropriate ADH secretion (SIADH) causing low sodium.

A form of external beam radiation that uses protons rather than X-rays. Protons have a unique physical property: they deposit most of their energy at a specific depth (the Bragg peak) and release very little beyond that point, unlike X-rays which continue travelling through the body after the target. This allows very high doses to the tumour while sparing adjacent normal tissue. Used for paediatric cancers, CNS tumours, head and neck cancers, prostate cancer, and tumours near critical structures.

A treatment using a photosensitiser drug that accumulates preferentially in cancer cells, then is activated by specific wavelengths of light delivered by a laser or LED. The light-activated photosensitiser generates reactive oxygen species (singlet oxygen) that destroy cancer cells directly and damage the tumour vasculature. PDT is used for superficial cancers (skin, oesophageal, lung airway, bladder, head and neck), pre-cancerous conditions (Barrett's oesophagus), and photodynamic diagnosis.

Platinum-based chemotherapy drugs that form cross-links within DNA strands, blocking DNA replication and triggering apoptosis — a form of alkylation. Key agents: cisplatin (first platinum drug, highly emetogenic, nephrotoxic), carboplatin (less nausea, less nephrotoxicity, but more bone marrow suppression), oxaliplatin (used in colorectal cancer — causes peripheral neuropathy, especially cold-induced), and nedaplatin (used in East Asia). Used in lung, ovarian, bladder, head and neck, testicular, colorectal, and cervical cancers.

Phase I trials are first-in-human studies testing a new drug or dose schedule, primarily assessing safety, tolerability, pharmacokinetics (how the drug is absorbed, distributed, metabolised, excreted), and finding the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D). Usually 15–50 patients, often with diverse cancer types. Phase II trials test whether the drug produces a meaningful anti-tumour effect at the Phase I dose, in a specific cancer type. Typically 50–200 patients; may be single-arm (no control group) or randomised.

Clinical trials conducted after a drug has received regulatory approval and is on the market. Phase IV trials monitor long-term safety, rare adverse events, effectiveness in broader real-world populations (including groups often excluded from Phase 3 trials: elderly, renally impaired, pregnancy), new indications, combination strategies, and pharmacoeconomics. Also called post-marketing surveillance or pharmacovigilance studies.

The gold standard of clinical evidence. Patients are randomly assigned (like a coin flip) to receive either the experimental treatment or the control (standard treatment or placebo). Randomisation eliminates selection bias. Blinding (where participants and/or investigators don't know which group they're in) further reduces bias. RCT results are expressed as hazard ratios (HR), p-values, and confidence intervals.

Treatment that uses high-energy radiation (X-rays, gamma rays, protons, or electrons) to damage the DNA of cancer cells, preventing them from dividing. Delivered either externally (external beam radiation therapy, EBRT) using a linear accelerator (linac), or internally (brachytherapy — radioactive seeds placed inside the body). Modern techniques — IMRT (intensity-modulated), IGRT (image-guided), VMAT — minimise damage to surrounding normal tissue. Typically given in multiple small doses (fractions) over weeks.

A phytochemical produced when cruciferous vegetables (broccoli, Brussels sprouts, kale, cabbage) are chopped or chewed — an enzyme (myrosinase) converts glucoraphanin into sulforaphane. It is one of the most studied natural anti-cancer compounds: activates NRF2 (master antioxidant pathway), inhibits HDAC (epigenetic mechanism), induces apoptosis in cancer cell lines, and inhibits NF-κB (inflammation). Highest concentration in broccoli sprouts (50–100× more than mature broccoli).

Cancer arising from mesenchymal (connective tissue) cells — bone, muscle, fat, cartilage, blood vessels, and nerves. Sarcomas are rare (~1% of adult cancers) and are classified into soft tissue sarcomas (e.g., liposarcoma, leiomyosarcoma, synovial sarcoma, rhabdomyosarcoma) and bone sarcomas (osteosarcoma, Ewing sarcoma, chondrosarcoma). They are treated at specialist sarcoma centres by multidisciplinary teams.

Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT, also called SABR) deliver very high doses of precisely targeted radiation in 1–5 sessions, using multiple beams converging on the target with millimetre accuracy. SRS is used for brain metastases and spinal tumours; SBRT for lung, liver, prostate, adrenal, and oligometastatic disease. Systems include Gamma Knife (SRS), CyberKnife, and standard linacs with SBRT capability.

Surgical removal of cancer tissue — the oldest and most direct cancer treatment. Resection aims to remove the entire tumour with a margin of normal tissue ('clear margins' or 'R0 resection'). Types: curative resection (intent to remove all cancer), debulking/cytoreductive surgery (remove as much tumour as possible, as in ovarian cancer), excision biopsy (remove the whole suspicious lesion), and minimally invasive approaches (laparoscopic, robotic). Margin status (R0=clear, R1=microscopic involvement, R2=gross residual) directly affects recurrence risk.

A measure of the total number of mutations per megabase (Mb) of DNA in a tumour. Expressed as mutations/Mb. TMB-high (typically ≥10 mut/Mb, with some using ≥10 or ≥16) predicts response to checkpoint inhibitors in some tumour types. Pembrolizumab is FDA approved for any TMB-high (≥10 mut/Mb) solid tumour (tumour-agnostic approval, 2020). High TMB means more neoantigens — a more immunogenic tumour.

Small-molecule drugs that block the activity of tyrosine kinases — enzymes that activate intracellular signalling cascades driving cell growth. TKIs enter cells (unlike antibodies, which work extracellularly) and competitively inhibit the ATP-binding site of kinases. Examples by target: EGFR TKIs (osimertinib, erlotinib, gefitinib), ALK TKIs (alectinib, brigatinib), BRAF TKIs (dabrafenib, vemurafenib), BCR-ABL TKIs (imatinib, dasatinib for leukaemia). Names often end in '-inib'.

The ecosystem surrounding a tumour — including cancer cells, immune cells (T cells, macrophages, NK cells, regulatory T cells), cancer-associated fibroblasts, blood vessels, and the extracellular matrix. The TME is not passive — tumours actively reshape it to create immunosuppression. 'Hot' tumours have inflamed TMEs rich in T cells and respond well to immunotherapy. 'Cold' tumours are immune-excluded and respond poorly.

A pathologist's assessment of how abnormal cancer cells look under the microscope compared to normal cells — reflecting how fast the cancer is likely to grow. Grade 1 (low grade, well-differentiated): cells look nearly normal, slow-growing. Grade 2 (intermediate): moderately differentiated. Grade 3 (high grade, poorly differentiated): cells look very abnormal, fast-growing. Some cancers use specific grading systems: Gleason score (prostate), Nottingham grade (breast), FIGO grade (gynaecological).

A class of chemotherapy drugs that stabilise microtubules — the protein scaffolding cells use to pull chromosomes apart during cell division. By locking microtubules in their assembled state, taxanes prevent cells from completing mitosis and trigger apoptosis. Agents: paclitaxel (Taxol), docetaxel (Taxotere), cabazitaxel (used after docetaxel in prostate cancer), nab-paclitaxel/abraxane (albumin-bound paclitaxel with better tumour penetration). Used extensively in breast, ovarian, lung, and prostate cancer.

See also the TKI entry in this glossary. TKIs are further subdivided by generation and target specificity. First-generation EGFR TKIs (erlotinib, gefitinib) are largely replaced by third-generation osimertinib (targets both sensitising EGFR mutations and T790M resistance mutation, with superior CNS penetration). Multi-target TKIs (cabozantinib, sunitinib) block multiple kinases (VEGFR, MET, RET) simultaneously. Resistance to TKIs is the primary challenge — usually developing within 1–3 years via secondary on-target mutations or bypass pathway activation.

A signalling protein secreted by tumours to stimulate the growth of new blood vessels (angiogenesis). VEGF binds to receptors on endothelial cells lining blood vessels, triggering their proliferation and migration to build the tumour's vasculature. Bevacizumab (Avastin) is a monoclonal antibody that traps circulating VEGF, preventing it from binding its receptors. VEGFR TKIs (sunitinib, pazopanib, axitinib) block the VEGF receptor intracellularly.

The observation by Otto Warburg (1927) that cancer cells preferentially ferment glucose into lactate even in the presence of oxygen (aerobic glycolysis) — unlike normal cells, which use efficient oxidative phosphorylation. Cancer cells use up to 200× more glucose than normal cells despite aerobic glycolysis being far less energy-efficient per glucose molecule. The Warburg effect is how PET scans find cancer (they detect high glucose uptake with FDG tracer).