Understanding Cancer

Colorectal cancer (CRC) arises from the inner lining (mucosa) of the colon or rectum, almost always from adenomatous polyps that gradually transform over 10–15 years. Molecular profiling is essential — RAS/RAF and MSI/MMR status fundamentally determine which systemic therapies will or will not work. Left-sided and right-sided tumours behave biologically differently: right-sided tumours are more commonly MSI-H and BRAF-mutant, while left-sided tumours more frequently benefit from anti-EGFR therapy.

Breast cancer is not one disease but a collection of distinct molecular subtypes with different prognoses and treatment strategies. The four main intrinsic subtypes — determined by ER, PR, HER2, and Ki67 — dictate treatment. Genetic testing (BRCA1/2, PALB2) is critical for surgical and systemic treatment decisions. Genomic assays (Oncotype DX, MammaPrint) help determine which early-stage hormone receptor-positive patients need chemotherapy.

Lung cancer is broadly divided into NSCLC (~85%) and SCLC (~15%). NSCLC is further classified histologically as adenocarcinoma (most common), squamous cell, and large cell. Molecular profiling is mandatory in all non-squamous NSCLC — over 10 actionable driver mutations are now targetable with approved drugs. PD-L1 expression guides immunotherapy selection. Never-smokers and former light smokers are more likely to harbour targetable mutations (EGFR, ALK, ROS1).

Prostate cancer ranges from indolent, low-risk disease (many men die with it rather than from it) to highly aggressive metastatic disease. Risk stratification using PSA, Gleason grade group, and clinical stage determines management — from active surveillance to immediate systemic therapy. Androgen receptor (AR) signalling drives almost all prostate cancer; BRCA2, CDK12, and ATM mutations define a subset with distinct biology and PARP inhibitor eligibility.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers — 5-year survival is ~12% overall due to late diagnosis and resistance to therapy. KRAS is mutated in ~95% of cases and drives the disease. Only ~15–20% are surgically resectable at diagnosis. Germline testing is essential — BRCA1/2 and PALB2 mutations identify PARP inhibitor eligibility. FOLFIRINOX and gemcitabine-nab-paclitaxel are the two main chemotherapy regimens.

Ovarian cancer is the deadliest gynaecological cancer — ~70% present at advanced stage (III-IV) because early-stage disease is often asymptomatic. High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype. BRCA1/2 and HRD (homologous recombination deficiency) testing is mandatory — these define PARP inhibitor eligibility, which has transformed maintenance therapy outcomes. Cytoreductive surgery ('debulking') followed by platinum-based chemotherapy is the cornerstone of treatment.

Melanoma arises from melanocytes and is the most lethal form of skin cancer. The two major therapeutic breakthroughs — BRAF/MEK targeted therapy and checkpoint immunotherapy — have transformed Stage IV melanoma from median OS of 6–9 months to >3 years in some populations. BRAF V600E mutation (present in ~50% of cutaneous melanoma) is the key biomarker determining treatment choice. Immunotherapy (anti-PD1 ± anti-CTLA4) benefits both BRAF-mutant and wild-type tumours.

Glioblastoma (GBM, WHO Grade 4) is the most aggressive primary brain tumour with a median survival of 14–16 months with standard therapy. The 2021 WHO CNS classification introduced molecular markers — IDH, MGMT, TERT, EGFR, 1p/19q — as defining features of brain tumour diagnosis, not just histology. MGMT promoter methylation is the most actionable biomarker — predicts benefit from temozolomide chemotherapy and certain clinical trials.