Inflammation and cancer:biology to targeted therapies

Describe the normal physiology of the respiratory system and the major pathological disease states and conditions which affect it. Using relevant examples encountered in this unit, demonstrate how the drug interacts with its biological target(s) Identify risk factors for developing lung cancer and understand the role of the pharmacist in health education to reduce lung cancer risk

what is Tumour formation

The development of abnormal cells that grow and divide uncontrollably, potentially leading to the formation of a tumor.

Genetic instability

The tendency of genetic material to undergo changes or mutations, which can contribute to the development of cancer.

how does inflammation initiate cancer formation

• inflammation can act as a tumour promoter

• Inflammation causes Genetic instability which leads to mutations

• Inflammation can exploit mutation in oncogenes supporting the onset of cancer

• Inflammation can reveal genes to be expressed and copied which shouldn't be - potentially cancer causing

• Inflammation can substitute several mutations which would result in cancer

What are Necrotic cells

Dead cells that have undergone cell death due to injury or disease.

what is Hypoxia

A condition characterized by reduced oxygen levels in tissues or organs.

how can hypoxia be caused in a tumour environment

• Immature blood vessels in tumour are prone to collapse, when collapse tumour cells surrounding blood vessels will no longer be supplied with oxygen

• Tumour cell growth can outstrip blood supply causing hypoxia as blood is only supplied to cell which is close to blood vessel

How can hypoxia benefit tumour growth

• When oxygen concentration decline in tumours leads to hypoxia- directed secretion of cytokines and chemokines which recruit tumour promoting immune cells and supress antitumor immune responses + cause angiogenesis

what is Angiogenesis

The formation of new blood vessels, often stimulated by factors released in response to hypoxia.

what is the tumour microenvironment

The surrounding environment in which a tumor grows, including factors such as blood vessels, immune cells, and extracellular matrix.

what contributes to tumour microenvironment

• Cancer cells

• Endothelial cells

• Fibroblasts

• Immune cells

• Secreted soluble growth factors

• Extra-cellular matrix

• Physiological and mechanical stress

what are Fibroblasts

Cells that produce and maintain the extracellular matrix, a network of proteins that support tissue structure.

what is repression of autoimmunity

The suppression or inhibition of the immune response against the body's own cells or tissues.

what is immune surveillance

• When tumours die they release antigens which are then presented on surface of cancer cells

• T-cells are primed + activated and migrate to site of tumour through blood vessels

• T cells then infiltrate tumour and recognise cancer cells and killed by T cells

what is Immunotherapy

The use of the immune system to treat or prevent diseases, such as cancer.

Immunosuppressive molecules

Molecules that inhibit or suppress the immune response, often produced by cancer cells to evade immune surveillance.

what are cancer signaling pathways

Intracellular pathways that regulate cell growth, division, and survival, often dysregulated in cancer.

Aim for Targeting STAT3

prevent changes in cancer and immune cells which result in immuno-suppressive tumour microenvironment

PD1 receptor

A receptor expressed on the surface of activated T cells that regulates immune responses.

PD-L1

A ligand expressed on dendritic cells or macrophages that interacts with the PD1 receptor to inhibit T cell activity.

Immune checkpoint inhibitors

Drugs that block the interaction between PD1 and PD-L1, allowing T cells to recognize and attack cancer cells.