Carcinogenesis & Mutations in Cancer

These flashcards cover key concepts regarding carcinogenesis and mutations in cancer based on the lecture notes.

What is carcinogenesis?

The process by which tumors appear, involving uncontrolled cell multiplication and new cellular capabilities such as invasion.

What are the different types of tumor invasion?

Local, regional, and metastatic.

What percentage of patients with malignant tumors die as a result of metastases or cancer complications?

90%.

What are the three phases of carcinogenesis?

Initiation, promotion, and progression.

What is required for the initiation of carcinogenesis?

The presence and action of an initiating factor, or carcinogenic agent.

What types of agents can act as carcinogens?

Chemical, physical, and biological agents.

What role do growth factors play in the promotion phase of carcinogenesis?

They act as promoting agents that ensure proliferation and the transmission of initiating mutations.

What defines tumor progression in carcinogenesis?

Acquisition of specific phenotypic characteristics by malignant cells, including uncontrolled growth and invasiveness.

What is the difference between driver mutations and passenger mutations in cancer?

Driver mutations are pathological and sufficient to trigger cancer, whereas passenger mutations are not consistently associated with cancer and may have unknown significance.

What are suppressor genes and how do they function in cancer?

Recessive genes that require two hits for cancer to develop, controlling processes involved in cell proliferation and survival.

How can mutations affect treatment strategies in oncology?

They can help identify specific targeted therapies and provide prognostic or predictive information.

What is tumor heterogeneity?

The presence of different clones within a tumor, leading to varying metabolisms and responses to treatment.

Why is early detection of cancer difficult?

Because identifying initiated cells often requires advanced techniques not currently available.

What is the significance of BRCA mutations in cancer?

They are involved in the repair of DNA errors and can be linked to several types of cancer, such as breast and ovarian cancers.

What is the relationship between age and cancer risk?

Age is a risk factor, but environmental factors and duration of exposure can have significant impacts as well.

What is the clinical implication of circulating tumor DNA (ctDNA)?

It can aid in monitoring treatment response and detecting recurrence as part of personalized treatment strategies.

What is carcinogenesis?

The process by which tumors appear, involving uncontrolled cell multiplication and new cellular capabilities such as invasion.

What are the different types of tumor invasion?

Local, regional, and metastatic.

What percentage of patients with malignant tumors die as a result of metastases or cancer complications?

90\%.

What are the three phases of carcinogenesis?

Initiation, promotion, and progression.

What is required for the initiation of carcinogenesis?

The presence and action of an initiating factor, or carcinogenic agent.

What types of agents can act as carcinogens?

Chemical, physical, and biological agents.

What role do growth factors play in the promotion phase of carcinogenesis?

They act as promoting agents that ensure proliferation and the transmission of initiating mutations.

What defines tumor progression in carcinogenesis?

Acquisition of specific phenotypic characteristics by malignant cells, including uncontrolled growth and invasiveness.

What is the difference between driver mutations and passenger mutations in cancer?

Driver mutations are pathological and sufficient to trigger cancer, whereas passenger mutations are not consistently associated with cancer and may have unknown significance.

What are suppressor genes and how do they function in cancer?

Recessive genes that require two hits for cancer to develop, controlling processes involved in cell proliferation and survival.

How can mutations affect treatment strategies in oncology?

They can help identify specific targeted therapies and provide prognostic or predictive information.

What is tumor heterogeneity?

The presence of different clones within a tumor, leading to varying metabolisms and responses to treatment.

Why is early detection of cancer difficult?

Because identifying initiated cells often requires advanced techniques not currently available.

What is the significance of BRCA mutations in cancer?

They are involved in the repair of DNA errors and can be linked to several types of cancer, such as breast and ovarian cancers.

What is the relationship between age and cancer risk?

Age is a risk factor, but environmental factors and duration of exposure can have significant impacts as well.

What is the clinical implication of circulating tumor DNA (ctDNA)?

It can aid in monitoring treatment response and detecting recurrence as part of personalized treatment strategies.

What is the 'two-hit hypothesis' (Knudson hypothesis)?

The principle that both alleles of a tumor suppressor gene must be inactivated (e.g., through mutation or deletion) to promote carcinogenesis.

What are examples of biological carcinogenic agents?

Viruses such as HPV (Human Papillomavirus), Hepatitis B and C, and certain bacteria like Helicobacter pylori.

What is the difference between a prognostic marker and a predictive marker?

A prognostic marker indicates the likely outcome of the disease regardless of therapy, while a predictive marker identifies the likelihood of response to a specific treatment.

How does clonal evolution contribute to tumor resistance?

As tumor cells divide, they acquire new mutations; therapy may kill sensitive cells but leave resistant clones to survive and multiply.

What is a 'Liquid Biopsy'?

A non-invasive diagnostic method that analyzes circulating

What is a 'Liquid Biopsy'?

A non-invasive diagnostic method that analyzes circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) from bodily fluids, such as blood, to monitor tumor evolution or treatment response.

What are examples of physical carcinogenic agents?

Ionizing radiation (e.g., X-rays and gamma rays), ultraviolet (UV) radiation, and mineral fibers like asbestos.

What are examples of chemical carcinogenic agents?

Polycyclic aromatic hydrocarbons (found in tobacco smoke), aflatoxins (produced by certain fungi), and alkylating agents used in some chemotherapies.

What is a proto-oncogene?

A normal gene involved in regulating cell growth and differentiation that can become an oncogene due to mutations or increased expression.

How do oncogenes differ from tumor suppressor genes in terms of mutation dominance?

Oncogenes usually result from a 'gain-of-function' mutation in a single allele (dominant), whereas tumor suppressor genes generally require 'loss-of-function' in both alleles (recessive) to promote cancer.

What is the role of angiogenesis in carcinogenesis?

The process by which a tumor recruits new blood vessels to provide the oxygen and nutrients necessary for its continued growth beyond a few millimeters.

What is telomerase and why is it important in cancer?

An enzyme that maintains telomere length, allowing cancer cells to avoid senescence and achieve 'cellular immortality' by dividing indefinitely.

What are the common steps of the metastatic cascade?

1. Local invasion
2. Intravasation (entering blood/lymph vessels)
3. Survival in circulation
4. Extravasation (exiting vessels into tissues)
5. Colonization and growth at a distant site

How does evasion of apoptosis contribute to tumor progression?

By disabling programmed cell death pathways (e.g., through mutation of the p53 gene), malignant cells survive even when they have significant DNA damage or are under physiological stress.

What is the 'Warburg Effect'?

A phenomenon where cancer cells preferentially use glycolysis for energy production even in the presence of oxygen (aerobic glycolysis), supporting rapid biosynthesis and growth.

What is the role of the tumor microenvironment (TME)?

The environment surrounding a tumor, including blood vessels, immune cells, fibroblasts, and the extracellular matrix, which can support or inhibit tumor growth and progression.

What is Epithelial-Mesenchymal Transition (EMT)?

A process by which epithelial cells lose their cell-cell adhesion and polarity, gaining migratory and invasive properties characteristic of mesenchymal cells, which is essential for metastasis.

How do cancer cells achieve immune evasion?

By expressing inhibitory proteins like PD-L1 that deactivate T-cells or by secreting immunosuppressive cytokines that dampen the host's immune response.

What are epigenetic modifications in carcinogenesis?

Changes such as DNA methylation or histone acetylation that alter gene expression without changing the DNA sequence, often leading to the silencing of tumor suppressor genes.

What is the difference between a benign tumor and a malignant tumor?

Benign tumors remain localized and do not invade surrounding tissues, whereas malignant tumors are invasive, grow rapidly, and have the potential to metastasize to distant organs.

What is the concept of synthetic lethality in cancer treatment?

A lethal phenotype that occurs when two specific genetic deficiencies are combined, such as using PARP inhibitors in patients with BRCA mutations whose cells already lack efficient DNA repair.

How does chronic inflammation contribute to the development of cancer?

By providing a persistent supply of growth factors, promoting angiogenesis, and inducing oxidative stress that results in DNA damage.

What is a 'cancer stem cell' (CSC)?

A specific subpopulation of cells within a tumor that possesses the capacity for self-renewal and can give rise to all the heterogeneous cell types found in the cancer.

What does the TNM staging system represent?

A standardized system where T describes the size of the primary tumor, N describes regional lymph node involvement, and M describes the presence of distant metastasis.

What is the role of mismatch repair (MMR) genes?

They are responsible for identifying and correcting errors in the DNA sequence that occur during replication; their loss leads to a state of high genomic instability.

What is the difference between tumor grade and tumor stage?

Grade refers to the histological appearance and degree of differentiation of cells, while stage refers to the physical extent and spread of the disease (TNM).

Why is the p53 gene known as the 'guardian of the genome'?

It monitors DNA integrity and prevents mutations by triggering cell cycle arrest for repair or inducing apoptosis if the damage is permanent.

What are paraneoplastic syndromes?

Distal clinical effects not caused by direct local tumor growth or metastases, but rather by tumor-secreted substances like hormones or immune-mediated responses.

What is 'oncogene addiction'?

A phenomenon where cancer cells become dependent on the continuous signaling of one specific oncogene for survival and proliferation.

What is a tumor marker?

A substance found in elevated amounts in the blood, urine, or tissues of some people with cancer, used to track disease progression or response to therapy.

What causes microsatellite instability (MSI)?

A defect in the DNA mismatch repair (MMR) pathway that leads to an accumulation of errors in short, repetitive DNA sequences.

What is lymphangiogenesis?

The formation of new lymphatic vessels from existing ones, providing a pathway for cancer cells to reach regional lymph nodes.

What does the 'seed and soil' hypothesis refer to in oncology?

The concept that cancer cells (seeds) can only develop into metastases in specific organs (soil) that provide a compatible environment.

What is cancer cachexia?

A metabolic syndrome characterized by progressive loss of skeletal muscle mass and adipose tissue, often leading to severe weight loss and weakness.

How does the loss of E-cadherin contribute to cancer progression?

It disrupts cell-to-cell adhesion, facilitating the detachment of tumor cells and promoting the epithelial-mesenchymal transition (EMT) required for invasion.

What is the Hayflick limit?

The maximum number of times a normal cell population will divide before reaching senescence, a barrier that cancer cells bypass by activating telomerase to achieve immortality.

Define Genomic Instability.

An increased tendency for DNA mutations and other genetic changes to occur during cell division, often resulting from defects in DNA repair and serving as a hallmark of cancer.

What is the difference between intravasation and extravasation?

Intravasation is the process by which tumor cells enter blood or lymphatic vessels, whereas extravasation is their exit from these vessels into the parenchyma of distant organs.

What are Tumor-Associated Macrophages (TAMs)?

Immune cells within the tumor microenvironment that can be 'reprogrammed' by the tumor to support growth, facilitate angiogenesis, and suppress the host immune response.

Explain the difference between germline and somatic mutations.

Germline mutations are inherited from parents and found in all cells of the body (BRCA1), while somatic mutations are acquired during life in specific cells and are not passed to offspring.

What is the concept of Multi-step Carcinogenesis?

The theory that cancer develops through the gradual accumulation of multiple genetic and epigenetic alterations in a single lineage of cells, leading to a malignant phenotype.

How does the Human Papillomavirus (HPV) contribute to carcinogenesis?

High-risk HPV types produce oncoproteins E6 and E7, which bind to and inactivate the tumor suppressor proteins p53 and Rb, respectively, disrupting cell cycle control.

What is Loss of Heterozygosity (LOH)?

A defining event in tumor suppressor gene inactivation where the remaining functional (wild-type) allele is lost, completing the 'two hits' required for functional inactivation.

What is a pre-cancerous (premalignant) lesion?

A benign but abnormal tissue growth, such as a polyp or dysplasia, that has an increased statistical probability of transforming into invasive cancer over time.

Define 'Metastatic Dormancy'.

A clinical stage where disseminated tumor cells survive at a distant site but do not increase in number, remaining in a quiescent state (G0 phase) for extended periods.