Adenoviruses and Herpes Virus Cancer Roles

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Questions and Answers

What is the primary role of E1A and E1B proteins in adenoviruses?

To promote viral replication and unregulated cell division (correct)

To enhance immune response

To induce cell apoptosis

To inhibit tumor growth

Which cancer is primarily associated with Epstein-Barr Virus (EBV)?

Burkitt's lymphoma (correct)

Breast cancer

Melanoma

Lung cancer

What mechanism does Epstein-Barr Virus (EBV) use to promote cancer?

It stimulates apoptosis in infected cells

It induces mitochondrial dysfunction

It enhances the differentiation of normal cells

It causes excessive proliferation of B lymphocytes (correct)

What key proteins are crucial for maintaining the cancerous state in cells infected by EBV?

EBNA proteins and latent membrane proteins (LMPs) Signup and view all the answers

Which other herpesvirus is known to cause Kaposi’s sarcoma?

Kaposi's Sarcoma-associated Herpesvirus (KSHV) Signup and view all the answers

What impact have herpesviruses had on cancer research and treatment?

They emphasize the role of persistent viral infections in cancer Signup and view all the answers

How do herpesviruses evade immune detection?

By expressing proteins that manipulate host cell growth control Signup and view all the answers

What is a common characteristic of herpesviruses in relation to infections?

They establish latent infections persisting for life Signup and view all the answers

What is the primary consequence of insertational mutagenesis?

Activation of oncogenes or inactivation of tumor suppressor genes Signup and view all the answers

Which chromosome translocation is associated with chronic myelogenous leukemia (CML)?

Chromosome 9 and 22 Signup and view all the answers

What is the role of the EGFR in cell signaling?

Promotes cell proliferation and survival Signup and view all the answers

Which mutations in the EGFR gene are commonly associated with non-small cell lung cancer (NSCLC)?

Exon 19 deletions and L858R point mutations Signup and view all the answers

How does the MYC translocation contribute to Burkitt’s lymphoma?

It leads to MYC overexpression and dysregulation of cell division. Signup and view all the answers

Which fusion gene is created due to the Philadelphia chromosome translocation?

BCR-ABL Signup and view all the answers

What effect do common EGFR mutations have in NSCLC?

They enable constant signaling for cell growth. Signup and view all the answers

What is a significant therapeutic target in chronic myelogenous leukemia due to the BCR-ABL fusion gene?

Tyrosine kinase inhibitors Signup and view all the answers

What is the main purpose of initiating mutations in cancer development?

They provide a foundation for further mutations. Signup and view all the answers

What distinguishes driver mutations from passenger mutations?

Driver mutations promote cancer progression. Signup and view all the answers

Which statement best describes cancer stem cells (CSCs)?

CSCs can differentiate into various tumor cell types. Signup and view all the answers

How do CSCs contribute to tumor heterogeneity?

By generating a diverse range of differentiated cells. Signup and view all the answers

What survival mechanism contributes to CSCs' resistance to traditional cancer therapies?

Efficient DNA repair mechanisms. Signup and view all the answers

What does clonal evolution in tumors refer to?

The ability of subclones to adapt to varying conditions. Signup and view all the answers

Which structural DNA variation involves large-scale changes such as deletions and duplications?

Structural variations. Signup and view all the answers

Why is targeting CSCs considered a beneficial strategy in cancer treatment?

They reduce tumor heterogeneity and prevent relapse. Signup and view all the answers

What role does telomerase play in cancer cells?

It allows cancer cells to divide indefinitely. Signup and view all the answers

Which characteristic is a hallmark of cancer related to telomerase?

Evasion of replicative senescence. Signup and view all the answers

How does c-Myc contribute to the regulation of telomerase in cancer cells?

By directly activating transcription of the TERT gene. Signup and view all the answers

What is a potential therapeutic approach related to telomerase in cancer treatment?

Blocking telomerase activity in cancer cells. Signup and view all the answers

What is the primary consequence of telomerase reactivation in cancer cells?

Extension of cellular lifespan. Signup and view all the answers

What percentage of cancers show activity of telomerase?

85-90% Signup and view all the answers

What effect does telomerase have on chromosomal stability in cancer cells?

It helps maintain chromosomal integrity. Signup and view all the answers

What is the mechanism by which c-Myc enhances cell proliferation in cancer?

By upregulating genes for cell cycle progression. Signup and view all the answers

What is the implication of the loss of APC function in colorectal cancer development?

It leads to the formation of polyps. Signup and view all the answers

Which of the following best describes the function of the VHL protein?

It aids in the degradation of hypoxia-inducible factor (HIF). Signup and view all the answers

What occurs as a result of mutations in the VHL gene in kidney cancer?

Accumulation of HIF leading to tumor growth. Signup and view all the answers

Familial Adenomatous Polyposis (FAP) is characterized by which of the following?

High risk of developing numerous polyps. Signup and view all the answers

How does the loss of tumor suppressor function contribute to cancer?

By disrupting critical cellular pathways. Signup and view all the answers

What is a consequence of mutant p53 in cancer cells?

Altered metabolic pathways supporting survival. Signup and view all the answers

What type of tumors are individuals with inherited VHL mutations predisposed to develop?

Hemangioblastomas and pheochromocytomas. Signup and view all the answers

Which therapeutic strategy may be effective in managing kidney cancer associated with VHL mutations?

VEGF inhibitors. Signup and view all the answers

Study Notes

Adenoviruses and Their Role in Cancer

Adenoviruses are DNA viruses that can cause respiratory infections and are linked to tumor development
Adenovirus E1A and E1B proteins promote viral replication and unregulated cell division, similar to the large T-antigen in SV40.
Studying adenoviruses has provided valuable insights into viral oncogenesis mechanisms and has led to advancements in gene therapy

Herpes Viruses and Their Role in Cancer

Herpesviruses are a family of DNA viruses, some of which are linked to cancers in humans.
Herpesviruses can establish latent infections.
Epstein-Barr Virus (EBV) causes Burkitt's lymphoma, nasopharyngeal carcinoma, and is associated with other lymphomas and cancers.
EBV infects B lymphocytes and can cause these cells to proliferate excessively, leading to cancer.
EBV proteins and RNA molecules manipulate the host cell's growth control to evade immune detection and promote cell survival.
EBNA (Epstein-Barr Nuclear Antigen) proteins and latent membrane proteins (LMPs) are critical for transformation and maintaining the cancerous state in infected cells.
Kaposi's Sarcoma-associated Herpesvirus (KSHV) causes Kaposi’s sarcoma, common in individuals with weakened immune systems.
KSHV induces cell transformation and promotes angiogenesis, supporting tumor growth.
Herpesviruses have highlighted the role of persistent viral infection in cancer development.
Herpesviruses demonstrate how viruses can evade immune responses, establish latency, and later reactivate, contributing to cancer in susceptible individuals, which has influenced approaches to immunotherapy and vaccine development.

Insertational Mutagenesis, Chromosomal Rearrangements, and Translocations

Insertational mutagenesis occurs when a viral or foreign DNA sequence integrates into the host genome, potentially near an oncogene or tumor suppressor gene.
This insertion can activate oncogenes or inactivate tumor suppressor genes, leading to uncontrolled cell division and cancer.
Retroviruses like HTLV-1 can integrate near oncogenes, driving cancerous growth through random insertions that disrupt gene regulation.
Translocations occur when parts of chromosomes are rearranged or exchanged, which can lead to gene fusions or dysregulation of important genes.
In Burkitt’s lymphoma, the MYC gene is translocated to a region near the immunoglobulin gene, resulting in MYC overexpression and uncontrollable cell division.
A chromosomal translocation between chromosomes 9 and 22 creates the BCR-ABL fusion gene in chronic myelogenous leukemia (CML).
This fusion gene encodes a constantly active tyrosine kinase that drives leukemic cell growth and proliferation, forming the basis for targeted therapies like imatinib (Gleevec) to inhibit BCR-ABL activity.

EGFR Mutations and Their Role in Non-Small Cell Lung Cancer (NSCLC)

EGFR (Epidermal Growth Factor Receptor) is a receptor tyrosine kinase that plays a critical role in cell proliferation, differentiation, and survival by activating pathways like RAS/MAPK and PI3K/AKT.
In non-small cell lung cancer, specific mutations in the EGFR gene lead to constant activation of the receptor, even without growth signals.
Common mutations in NSCLC include exon 19 deletions and L858R point mutations in exon 21, which alter the receptor’s configuration, enabling constant signaling for cell growth.

Telomeres and Their Role in Cancer: Replicative Senescence and Immortalization

Telomeres are protective caps at the ends of chromosomes that shorten with each cell division.
Replicative senescence is a process in which cells stop dividing after a certain number of divisions due to telomere shortening.
Cancer cells often reactivate telomerase, allowing them to bypass replicative senescence and evade the Hayflick limit.
Telomerase is active in approximately 85-90% of cancers, underscoring its essential role in tumor growth.

Therapeutic Targeting of Telomerase

Since telomerase is mostly inactive in normal cells but reactivated in most cancer cells, it serves as a potential target for anti-cancer therapies.
Therapies aimed at inhibiting telomerase activity, blocking TERT expression, or targeting telomerase’s function in maintaining telomeres are under investigation.

Regulation of Telomerase Expression by Oncogenes like c-Myc

c-Myc is a transcription factor that regulates genes involved in cell growth, metabolism, and proliferation.
c-Myc directly binds to the promoter region of the TERT gene (encoding the catalytic subunit of telomerase) and activates its transcription.
c-Myc upregulates TERT expression, thereby increasing telomerase activity in cells where it is normally low or absent.

Late Mutations in Cancer Development

Initiating Mutations occur early in the development of a tumor and often involve tumor suppressor genes or DNA repair genes.
Driver mutations promote cancer progression but passenger mutations do not contribute directly, but can increase overall genetic instability.

Cancer Stem Cells (CSCs) and Their Role in Tumor Heterogeneity

Cancer stem cells a subpopulation of cancer cells with stem cell-like properties, including the ability to self-renew and differentiate into various cell types within the tumor.
CSCs can arise from normal stem cells or from differentiated cells that acquire mutations enabling stem-like behavior.
CSCs give rise to a range of differentiated cells within the tumor, creating tumor heterogeneity.
CSCs contribute to clonal evolution, allowing different subclones to adapt to various conditions, such as nutrient availability or therapeutic interventions.
Many tumors are organized hierarchically, with CSCs at the top, generating other cell types that make up the bulk of the tumor.

Resistance to Therapy by Cancer Stem Cells

CSCs are often resistant to traditional cancer therapies due to their efficient DNA repair, quiescence, and drug-efflux pumps.
After therapy, CSCs can survive and regenerate the tumor, leading to relapse or metastasis.
Targeting CSCs specifically, alongside other cancer cells, is a strategy to reduce tumor heterogeneity and improve long-term treatment outcomes by preventing recurrence.

Structural DNA Variations Leading to Tumor Formation

Structural variations involve large-scale changes in DNA structure, including deletions, duplications, inversions, translocations, and copy number variations (CNVs).
Loss of APC function is an early event in the development of colorectal tumors, leading to the formation of polyps and, eventually, malignant tumors.
Familial Adenomatous Polyposis (FAP): Individuals with inherited APC mutations develop numerous polyps and have a high risk of colon cancer.

VHL (Von Hippel-Lindau) in Kidney Cancer

The VHL protein is a tumor suppressor that regulates the degradation of hypoxia-inducible factor (HIF), a protein involved in cellular responses to low oxygen levels.
Under normal oxygen conditions, VHL tags HIF for degradation, maintaining low HIF levels and preventing uncontrolled cell growth and angiogenesis.
Mutations in VHL: In renal cell carcinoma, loss of VHL function leads to the accumulation of HIF, which activates genes involved in angiogenesis and cell proliferation, promoting tumor growth.
VHL mutations contribute to clear cell renal cell carcinoma, a common type of kidney cancer.
Von Hippel-Lindau Disease: Inherited VHL mutations predispose individuals to multiple tumors, including kidney cancer.

Implications of Tumor Suppressor Loss

The loss of APC and VHL exemplifies how inactivation of tumor suppressors can disrupt critical cellular pathways, promoting unregulated cell growth and tumorigenesis.
Understanding these pathways has led to targeted therapies, such as VEGF inhibitors for kidney cancer and Wnt pathway inhibitors in colorectal cancer, designed to counteract the effects of tumor suppressor loss.

Mutant p53’s Role in Enhancing Cancer Cell Metabolism and Survival

While wild-type p53 typically acts to suppress tumor growth, mutations in p53 not only disable its tumor-suppressing functions but also contribute to metabolic adaptations that support cancer cell survival.

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Description

Explore the connections between adenoviruses, herpes viruses, and cancer development. This quiz delves into how these DNA viruses influence tumorigenesis through mechanisms like viral replication, cell division, and immune evasion. Test your knowledge on the role of viruses in oncogenesis and gene therapy advancements.