Summary Flashcards
Give 3 examples of oncogenes and explain their function and pathways they regulate and how they drive cancerogenesis forward
RAS genes encode for GTPase proteins that in cancer promote proliferation and surrvuval through the MAPK and P13-AKT signalling pathways.
MYC encodes for transcriptional factors that enhances gene expression of genes that regulate cell cycle progression and metabolism through pathways such as WNT and P13K which promotes cell differentiation, surrvival etc.
HER2 is a growth factor that binds to receptor tyrosine kinases which promotes cell proliferation, surrvival, differentiation etc.
Describe 2 tumor supressor genes, their function and how they can promote cancerogenesis and how can we target them in cancer therapy
P53 also known as the guardian of the genome regulated the cell cycle in G1/S checkpoint in case of DNA damage which is before DNA replication which inhibits propagation of mutations. It can initiate DNA repair pathways by activating genes, and in case of severe DNA damage it can initiate apoptosis by activating pro-apoptopic proteins such as BAX, BAK and PUMA and repress anti-apoptopic factors such as BCL-2. In cancer is van get loss of function mutations, promoter can become hypermethylated or mutations which alters the amino acid sequence so the protein is faulty or can even be tumorogenic which inhibits it’s tumor supressor functions. Gene therapy to introduce a functional TP53 in cancer cells, small molecules that can reactivate or mimic it’s function to promote cancer cell death and immunotherapy with the function to kill P53 defiecent cells is an option.
PTEN regulates the P13K/AKT pathway by dephosroylating PIP3 which prevents AKT activation and this regulating cell growth, differenitation etc. It can develop loss of function mutations that silences it and theraputic targets include inhibiing the P13/AKT pathway again.
What are some stel cell markers and what properties does it contribute with?
Stem cell cancer markers include CD44 which is a cell surface glycoprotein that is involved in cell-cell interactions, cell adhesion and migration. It is linked to cancer progression and metastasis. CD133 is a membrane protein that can be used as a marker to identify and isolate cancer stem cells, especially in colorectal, liver and brain cancer. ALDH is an enzyme that is highly expressed in cancer stem cells and correlate with tumorigenic potential and resistance to chemotherapy. Oct4 is a transcription factor that plays a key role in maintain pluripotency and self renewal in stem cells and is often overexpressed in cancer stem cells.
Why is cancer stem cells more therapy resistant?
During cell stress it can enter a quiescent state which eliminates it as a target for chemotherapy that targets rapidly dividing cells, it overexpresses ABC-transporters which are drug efflux transporters, and it has enhanced DNA repair mechanisms such as homologous recombination and non homologous end joining pathways.
How can we target CSC in treatment?
Focusing on the signalling pathways Notch, WNT and Hedgehog which they are regulated by to eliminate them.
Describe correlation between cancer stem cells (CSC) and circulating tumour cells (CTC). How and where are the CTC detected in a patient?
Circulating tumor cells are cells that have shed from the tumor and circulates in the body which can have stem cell proprties or be cancer stem cells. This is of importance since only stem cells can initiate tumors on a new site which means it’s a higher risk of metastasis. They can be detected by immunoaffinity assays which uses antibodies targeted for the CTC or size based filtration as the cells are bigger compared to normal red blood cells.
How can we study CSC?
We can isolate them based on their cancer stem cells markers and isolate them from the bulk tumor population using flow cytometry. We can also use sphere formation assays which are cell cultures without adhesion and serum free medium as primarly CSC can grow spheres under those conditions. Once isolated they can also be injected in immunosupressed xenograph models such as mice and analyze their tumor initiation ability.
What does the telomerase activity look like during normal and cancer cells compared?
Normal cells have TERC active always shich is the RNA component of telomerase but inactive TERT gene which encodes the catalytic subunit of telomerase. Cancer cells have both these active always.
Give 3 examples of cancer types and specific examples of cancers within that type
Carcinoma comes from epithelial cells and examples include adenocarcinoma, squamois cell carcinoma.
Sarcomas originate from mesenchymal cells and examples are osteosarcoma and liposarcoma.
Leukemias comes from hematopoietic stem cells and examples include acute myeloid leukemia and acute lymphoblastic leukemia.
How can we detect tumor heterogeneity?
Single cell RNA sequencing which looks at gene expression of idnevidual cells within the tumor or between the tumors, and immunohistochemistry which looks at differences in protein expression between tissuesections of the tumor.
Describe how methylation occurs
Substrate Recognition: DNMTs recognize specific cytosine residues in the DNA sequence, typically within CpG dinucleotides.
Methyl Group Transfer: DNMTs transfer a methyl group from SAM to the 5th carbon position of the cytosine ring, resulting in the formation of 5-methylcytosine.
What are the two types of radiation therapy called?
External Beam Radiation Therapy (EBRT): This uses high-energy beams (like X-rays or gamma rays) directed at the tumour from outside the body.
Brachytherapy: This involves placing a radioactive source directly inside or next to the tumour, delivering a high radiation dose to the tumour while sparing surrounding healthy tissues.
Name 3 immune parameters that can serve as biomarkers in cancer
Tumour-Infiltrating Lymphocytes (TILs): The presence and abundance of TILs in the tumour microenvironment can indicate the immune response against the tumour. Higher TIL levels are often associated with better prognosis and response to immunotherapy.
Programmed Death-Ligand 1 (PD-L1) Expression: PD-L1 expression on tumour cells can suppress immune responses. High PD-L1 levels are used as a biomarker for selecting patients who might benefit from immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 therapy).
Cytokine Profiles: Levels of cytokines such as interleukins (e.g., IL-6, IL-10) and interferons (e.g., IFN-γ) in the blood or tumour microenvironment can reflect the immune status and inflammation associated with cancer.
IL-6: Pro-inflammatory, Promotes tumourigenesis by stimulating cell proliferation and survival. Involved in angiogenesis and metastasis.
IL-10: Anti-inflammatory, Suppresses immune responses to avoid excessive tissue damage, In cancer, IL-10 may promote tumour immune escape by inhibiting antitumour immunity. Elevated IL-10 levels can correlate with poor prognosis in some cancers.
Describe how Microenvironment and cancer work together in cancer development, progression and/or metastasis.
Cancer cells interact dynamically with their microenvironment, consisting of stromal cells, immune cells, extracellular matrix (ECM), and signaling molecules, to promote development, progression, and metastasis.
Interaction with Fibroblasts: Cancer-associated fibroblasts (CAFs) secrete growth factors like TGF-β and VEGF, promoting tumour growth, angiogenesis, and invasion. CAFs also remodel the ECM, creating pathways for cancer cell migration and metastasis.
Immune Cell Manipulation: Cancer cells recruit and reprogram immune cells like macrophages into tumour-associated macrophages (TAMs). TAMs release cytokines (e.g., IL-10, IL-6) that suppress anti-tumour immune responses and stimulate angiogenesis, aiding in tumour growth and immune evasion.
How is apoptosis regulated by surrvival signals?
Survival signals (e.g., PI3K/Akt pathway) can block apoptosis by inhibiting pro-apoptotic proteins like Bax and activating anti-apoptotic proteins like Bcl-2.
