Cancer

Question 1

What are the primary hallmarks of cancer?

Answer 1

Sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis.

Question 2

What are other key hallmarks of cancer?

Answer 2

Enabling replicative immortality, inducing angiogenesis, and resisting cell death

Question 3

What does “oncogene addiction” refer to in cancer?

Answer 3

: It refers to tumors that become dependent on specific oncogenes, such as EGF, while others are not.

Question 4

What are Receptor Tyrosine Kinases

Answer 4

Growth factor receptors and single transmembrane receptors involved in signaling pathways.

Question 5

What is the EGF proliferation pathway?

Answer 5

EGF ➔ dimerization ➔ autophosphorylation ➔ Grb2 ➔ Sos ➔ Ras ➔ Raf ➔ MEK ➔ MAPK ➔ proliferation

Question 6

How does the evasion of apoptosis occur in cancer?

Answer 6

: EGF ➔ dimerization ➔ autophosphorylation ➔ PI3K ➔ AKT ➔ evasion of apoptosis

Question 7

What is AKT’s role in cancer

Answer 7

AKT is a central activation molecule common in most cancers

Question 8

What are ErbB2 and ErbB4 associated with

Answer 8

ErbB2 is Her2 in breast cancer, while ErbB4 is associated with cardiac functions

Question 9

How do anti-EGFR drugs work?

Answer 9

They bind to the EGF binding domain, preventing ligand binding, and downregulate all signaling pathways from that receptor.

Question 10

What is the main Fab-dependent action of monoclonal antibodies in cancer treatment?

Answer 10

They inhibit proliferative/survival signaling

Question 11

What is the Fc-dependent action of monoclonal antibodies

Answer 11

Antibody-dependent cellular cytotoxicity (ADCC), which recruits immune cells to kill tumor cells.

Question 12

How does Trastuzumab target HER2 in breast cancer?

Answer 12

: It binds HER2, blocks dimerization, activates ADCC, causes tumor cell lysis, and degrades HER2.

Question 13

How can Trastuzumab’s effectiveness be improved

Answer 13

By cross-linking it with toxins to inhibit microtubules, improving effectiveness and reducing recurrence.

Question 14

What are the two main types of cancer resistance mechanisms

Answer 14

Intrinsic resistance and acquired drug resistance.

Question 15

What is intrinsic resistance in cancer

Answer 15

Pre-existing resistance factors in tumors cause treatment to be ineffective

Question 16

How does acquired drug resistance develop in cancer?

Answer 16

Through mutations, drug target changes, or alternate signaling pathways in response to treatment.

Question 17

How can epigenetics lead to drug resistance in cancer?

Answer 17

Changes in DNA methylation can alter gene expression, making the cancer less responsive to treatment.

Question 18

What is drug efflux in the context of cancer resistance

Answer 18

Cancer cells express pumps that actively pump out cancer drugs.

Question 19

: How does DNA damage repair contribute to cancer resistance

Answer 19

Cancer cells repair DNA damage caused by treatments like chemotherapy and radiation.

Question 20

How do cancer cells inhibit cell death to resist treatment?

Answer 20

They use anti-apoptosis mechanisms to survive despite treatments that aim to induce apoptosis.

Question 21

What role does epithelial-mesenchymal transition play in cancer resistance

Answer 21

Cancer cells switch between states to avoid targeted therapies

Question 22

What is drug target alteration in cancer resistance?

Answer 22

Mutations (gatekeeper mutations) hinder drug binding, like with imatinib

Question 23

How do cancer cells use alternative pathways to resist treatment

Answer 23

They bypass targeted pathways using other signaling routes to maintain growth

Question 24

What is tumor heterogeneity, and how does it impact treatment?

Answer 24

Genetic and phenotypic variations in cells mean some cells survive treatment, leading to recurrence.

Question 25

How does the tumor microenvironment affect treatment success?

Answer 25

Stromal cells can secrete factors that protect cancer cells; in some cases, AB therapy resistance is addressed with fecal matter replacement

Question 26

What is the role of c-Kit mutations in cancer?

Answer 26

They contribute to proliferative tumors, especially in cancers like mast cell tumors and certain lymphomas.

Question 27

What are Gastrointestinal Stromal Tumors, and what are common treatments?

Answer 27

GISTs are soft-tissue sarcomas often treated with surgery and imatinib, targeting KIT and PDGFR mutations

Question 28

What is the role of C-Met/HGFR in cancer

Answer 28

It’s targeted to prevent metastasis

Question 29

How does immunotherapy help in cancer treatment

Answer 29

It increases immune activation and decreases immune suppression caused by tumors.

Question 30

What are the two types of immunotherapy responses

Answer 30

Adaptive (responds to new agents) and innate (first-line defense with proteins and cells).

Question 31

How does anti-PD1 mAb work in immunotherapy

Answer 31

: It blocks PD-1 interaction with PD-L1/PD-L2 on tumor cells, allowing T-cells to attack the tumor

Question 32

How do tumor cells use PD-L1 to evade the immune system?

Answer 32

PD-L1 on tumor cells binds PD-1 on T-cells, inhibiting immune response

Question 33

How do Antibody-Drug Conjugates (ADCs) kill cancer cells

Answer 33

They bind to antigens, undergo endocytosis, release cytotoxic drugs in lysosomes, and induce apoptosis

Question 34

What are different types of nanoparticle delivery systems in cancer treatment

Answer 34

Lipid-based, polymer-based, inorganic nanoparticles, viral nanoparticles, and drug conjugates.

Question 35

How does passive nanoparticle targeting work

Answer 35

Nanoparticles exploit fenestrated vasculature, common in rapidly growing tumors

Question 36

What is active nanoparticle targeting

Answer 36

It uses ligands on nanoparticles to target specific cell types, like those marked with luciferase siRNA.

Question 37

What is a hypoxic area in tumors?

Answer 37

A region with no blood supply, often resistant to therapy.

Question 38

: How do cancer stem cells differ from non-CSCs?

Answer 38

CSCs are chemo-resistant, while non-CSCs have higher mitochondria and reactive oxygen species.

Question 39

What are examples of next-generation cancer treatments?

Answer 39

ATRA (all-trans retinoic acid) and CPT (Camptothecin).

Question 40

: How do ATRA and CPT work in cancer stem cells

Answer 40

They induce differentiation and cytotoxicity through structural changes and reactive oxygen species elevation.

Question 41

How do CTLA-4 and PD-1 differ in immune regulation?

Answer 41

CTLA-4 inhibits early immune response in lymph nodes; PD-1 regulates response in peripheral tissue.

Question 42

What is the role of MHC in cancer immunotherapy?

Answer 42

MHC presents tumor-derived peptides to T-cells for immune recognition

Question 43

What are the steps of the cancer immunity cycle?

Answer 43

1. Release antigens, 2. Antigen presentation, 3. T-cell priming, 4. T-cell trafficking, 5. Infiltration, 6. Recognition by T-cells, 7. Cancer cell killing.

Question 44

What pathway drives muscle wasting in cancer cachexia, and what protein can block this process?

Answer 44

The SMAD2/3 pathway drives muscle wasting through Myostatin and Activins; Follistatin can block this pathway.

Question 45

What proteins inhibit the BMP pathway, impacting muscle growth regulation in cancer cachexia?

Answer 45

Noggin, Chordin, and Gremlin.

Question 46

Define cancer cachexia.

Answer 46

Cancer cachexia is the unintentional loss of skeletal muscle, often with fat loss, associated with chronic disease, not reversible by nutritional support.

Question 47

What percentage of advanced cancer patients die due to cachexia?

Answer 47

30%.

Question 48

Describe the main features of cancer cachexia

Answer 48

Cancer cachexia is multifactorial, causing anorexia, cardiac atrophy, lipolysis, muscle atrophy, and weakness due to systemic inflammation

Question 49

What occurs in proteostasis imbalance in cancer cachexia?

Answer 49

There is an increase in catabolic processes and inhibition of anabolic muscle growth

Question 50

Outline the pro-inflammatory pathway in classic signaling in cancer cachexia

Answer 50

IL-6 binds to IL-6R → recruits gp130 → activates JAK kinase → STAT3 → drives inflammation and muscle atrophy.

Question 51

How does the trans-signaling pro-inflammatory pathway affect cancer cachexia?

Answer 51

IL-6R is cleaved, becomes soluble, binds IL-6, recruits gp130, activates JAK kinase, and drives inflammation.

Question 52

What role does the IGF-AKT pathway play in cancer cachexia?

Answer 52

It promotes protein synthesis and reduces degradation, helping to counter muscle atrophy.