Introduction to Carcinogenesis and Cancer Hallmarks

Introduction to Carcinogenesis

• Non-Hodgkins lymphoma is a type of cancer
• Radiolabeled fluorodeoxyglucose (FDG) is used in PET scans
• PET scans are used in medical imaging

Hallmarks of Cancer

• Cancer research has revealed that cancer involves dynamic changes in the genome
• The hallmarks of cancer are six biological capabilities acquired during the development of human tumors
• These hallmarks organize the complexities of neoplastic disease
• Examples of hallmarks: sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis

Carcinogenesis: Introduction

• Cancer has a significant impact
• Some definitions of cancer include: benign tumors (neoplastic cells remain clustered together in a single mass), malignant tumors (cancer cells have acquired the ability to invade surrounding tissue)
• Hallmarks of cancer are an important concept for understanding this disease
• Literature references include: "Hallmarks of Cancer: The Next Generation" (Cell 2011, pg 646-654) and chapter 20 of MBC 6th Edition (pgs 1091-1126)

Some, not so nice, numbers

• An estimated 2.7 million new cases of cancer and 1.3 million deaths from cancer occurred in Europe in 2022
• The most common cancer sites were female breast, colorectal, prostate, and lung cancers
• The most common causes of cancer death were lung, colorectal, breast, and pancreatic cancers

Cancer is an age-related disease

• The incidence of cancer increases with age across all sexes and cancer types

20-Year Lag Time Between Smoking and Lung Cancer

• Cigarette consumption (men) increased gradually over decades
• Lung cancer deaths (men) increased after a 20-year delay mirroring cigarette consumption patterns

Why are lung cancer rates still rising for women?

• The percentage of women smoking increased as rates rose for lung cancer
• The number of women smokers and lung cancer rates have both continued to rise

Breast Cancer Incidence Worldwide

• Age-standardized rates of breast cancer incidence differ significantly across countries showing significant variations

Breast Cancer Mortality Worldwide

• Age-standardized rates of breast cancer mortality differ significantly across countries showing significant variations

Breast cancer

• One in eight women will develop breast cancer during their lifetime
• The graphic illustrating one in eight needs improvement to be more accurate.

Cancer survival increases

• Overall cancer survival rates for both sexes and each individual gender have increased over time

For most cancers survival improved!

• 5-year survival rates have improved over time across many cancer types

Some definitions

• Leukemia: cancer arising from white blood cells
• Lymphoma: cancer arising from lymph nodes
• Carcinomas: cancer arising from epithelial cells (e.g., skin, breast, lung)
• Sarcomas: cancer arising from connective tissue or muscle cells, such as bone and soft tissue

How many mutations are necessary to transform normal cells into cancerous cells?

• Mutations are necessary for transforming normal cells into cancerous cells

Six changes are needed to cause cancer

• Six hallmarks have been found that are essential to the development of multiple cancers. These include resisting cell death, inducing angiogenesis, sustaining proliferative signaling, enabling replicative immortality, evading growth suppressors and activating invasion and metastasis

Most prominent feature is:

• Hallmarks are grouped into circuits including motility, proliferation, cytostasis/differentiation, and viability to show their relationships to each other and to other characteristics of cancer

Removal of the brake:

• The same characteristics are grouped into circuits according to how they work together. These include motility, proliferation, cytostasis/differentiation, and viability, to show their relationships to each other and to other aspects of cancer

The importance of P53:

• P53 is an important characteristic in cancer development

Unlimited replicative potential:

• Telomeres are extremely important in allowing cancer cells to continue to replicate.

Tumors need food!

• Tumors require blood vessels to provide nutrients and oxygen
• Vascular endothelial growth factor (VEGF) is important in tumor growth

Loss of adhesion molecules:

• Adhesion molecules are critical for preventing cancer spread
• The loss of adhesion creates a mechanism for cancer cells to metastasize

Acquired Capability / Example of Mechanism

• A chart showing what mechanisms cause acquired cancer capabilities
• The chart is composed of different acquired capabilities, each with their own description of the mechanisms responsible

Cellular causes for cancer development

• Overactivity of Growth Promoting events (e.g., GF signaling, factors)
• Underactivity or Growth Inhibitory events (e.g., DNA repair, apoptosis)

The cancer genes

• Oncogenes are overactive genes that cause normal cells to grow
• Tumor suppressors are genes that help prevent cancer growth
• Mutations in these genes can lead to cancer development

Emerging Hallmarks

• Deregulating cellular energetics and avoiding immune destruction have been shown to play a role in cancer

Understanding the Warburg effect

• A change in how cells use glucose to produce energy
• Cancer cells primarily use glycolysis for energy

Evading immune destruction

• A key characteristic of cancer cells is their ability to avoid detection and destruction by the immune system
• Tumor cells often lack or alter the expression of tumor-specific antigens recognized by T cells

Enabling characteristic, tumour promoting inflammation

• Inflammation is a key enabling characteristic of cancer
• Inflammation can provide bioactive molecules that promote cancer growth, angiogenesis, and survival

Enabling characteristic, genomic instability

• Genomic instability is a key enabling characteristic of cancer
• There is an increased rate of mutations in tumor cells due to breakdown in maintenance machinery and compromised surveillance systems

Therapeutic Targeting

• A diagram showing how targeted therapies aim at manipulating the hallmarks

Explore the key concepts surrounding carcinogenesis and the hallmarks of cancer in this informative quiz. Understand the implications of PET scans in cancer detection and the biological capabilities that define tumor development. Enhance your knowledge of cancer biology and its complexities.