Cancer and Inflammation Overview

Cancer and Inflammation

• Inflammation is intrinsically linked to cancer.
• Targeting cancer-associated inflammation is a therapeutic approach.
• Understanding the link between cancer, inflammation and symptoms can help identify potential cancer "red flags".
• Knowledge of this link is integrated into clinical practice.

Cancer in the UK

• One in two people will be diagnosed with cancer in their lifetime.
• Cancer survival has doubled since the 1970s.

What Makes a Cancer Cell Different?

• Cancer cells arise from mutations.
• These mutations occur frequently.
• The body is well-equipped to handle these mutations.

What Makes a Cell Cancerous?

• Evasion of apoptosis
• Tissue invasion and metastasis
• Insensitivity to growth inhibitors
• Sustained angiogenesis
• Limitless replicative potential
• Self-sufficiency in growth signals
• An inflammatory microenvironment

Tumour-Promoting Inflammation

• Inflammation supports all aspects of cancer.
• This includes initiation, growth, metastasis and response to therapy.

Inflammation: Cancer Initiation

• Chronic inflammation initiates tumour formation.
• Chronic inflammation causes genetic instability, leading to mutations.
• Chronic inflammation exploits existing mutations (oncogenes).

Inflammation: Tumour Growth

• Immune cells produce factors, supporting all facets of tumour progression.
• Immune cells and tumour cells have a positive feedback loop; encouraging tumour progression.

Inflammation: Metastasis

• Pro-tumourigenic inflammation supports the degradation of the extracellular matrix (ECM) and intravasation.
• Pro-tumourigenic inflammation facilitates pre-metastatic niche formation, attraction to the metastatic site, and subsequent extravasation.
• Inflammation is involved in the growth and development of metastases.

Expanded Hallmarks of Cancer

• Tumor-promoting inflammation as a hallmark of cancer survival.

Anti-tumour Immunity (Inflammation)

• Immunization, antigen processing and antigen uptake are crucial parts of the anti-tumour immune response.
• Cells like dendritic cells and cytotoxic T cells play a key role in recognizing and eliminating tumour antigens.
• Regulatory T cells and immune checkpoints, such as PD-L1, regulate the anti-tumour immune response, aiming to avoid damaging the body’s own healthy cells.

Balance of Pro and Anti-tumour Immunity

• Pro-and anti-tumour immunity is in a delicate balance.
• Tumor cells and inflammatory cells work together in a positive feedback loop maintaining tumour growth

Inflammatory Risk Factors for Cancer

• Obesity.
• Smoking.
• Alcohol consumption.
• Chronic inflammatory diseases.
• Genetics.

Cancer Causation

• Many cancers are preventable.
• Key risk factors include tobacco use, overweight/obesity, diet low in fruits and veggies, low fiber diets, alcohol, inactivity, and infections.
• Prevention strategies like avoiding tobacco, maintaining a healthy weight, and a varied diet are crucial.

Obesity and Cancer

• Obesity can lead to cancer via several pathways.
• These include increased estrogen after menopause, excess insulin and growth factors, and inflammation.

Inflammatory Signalling and Cancer

• Lifestyle factors like high-fat diets, tobacco use, infections, stress, environmental pollution and radiation exposure can lead to inflammation signaling influencing cancer development and progression.
• Inflammation-related biomarkers like cytokines (IL-1, IL-6, IL-8, IL-17, TNF-α, COX-2, 5-LOX, CRP, PSA) and STAT3 activation are associated with different types of cancer and related diseases.
• Chronic diseases like cancer, diabetes, cardiovascular diseases, and pulmonary diseases can be linked to inflammation signaling and certain lifestyle choices.

Inflammation and Cancer

• Inflammation plays a role in different stages of cancer development, from initiation to metastasis and resistance to treatment.
• Inflammation can be both a cause and a consequence of cancer.

Targeting Inflammation for Cancer Therapy

• Two approaches for targeting inflammation are available.
• The first approach is inhibiting pro-tumour inflammation.
• The second approach is promoting anti-tumour inflammation

Targeted Therapies: Inhibiting pro-tumour Inflammation

• Signalling pathways and molecules involved in promoting inflammation are targeted using inhibitors.
• Example: B-raf inhibitors target inflammation-related signal pathways to prevent tumour growth.

Immunotherapy: Promoting Anti-tumour Inflammation

• Immune checkpoints are targeted by drugs, resulting in anti-tumour T-cell-mediated immune responses.
• Examples: Anti-CTLA-4 and Anti-PD-1 therapies.

Cancer Red Flags

• Red flags are symptoms indicative of cancer, prompting immediate medical assessment.
• These symptoms should be considered alongside other risk factors and patient history.

Assessing Cancer Red Flags

• Duration of symptoms is critical for considering them as genuine cancer "red flags."
• Symptoms' severity and longevity, along with other risk factors, guide healthcare decisions.
• Unexplained lumps, bleeding, or mucosal abnormalities are notable and warrant immediate investigation.

Red Flag Symptoms - Examples

• Persistent cough, coughing up blood, recurrent chest infections (Lung cancer), red or white patches in the mouth or neck, unexplained lumps.