Pathophysiology of gene expression Flashcards
- refers to the abnormal functioning or dysregulation of gene expression, leading to various physiological or
pathological conditions. - it is the process by which the information encoded in a gene is turned into a function. This mostly occurs via the transcription of RNA molecules that code for proteins or non-coding RNA molecules that serve other functions.
GENE EXPRESSION
- There are many proteins that are turned on or off (gene activation or gene silencing) that dramatically alter the overall activity of the cell.
-A gene that is not normally expressed in that cell can be switched on and expressed at high levels. This can be the result of gene mutation or
changes in gene regulation ( epigenetic, transcription, post-transcription, translation, or post-translation).
GENE EXPRESSION
- The onset and spread of cancer are significantly influenced by gene expression.
- Cancer can be described as a disease of altered gene expression.
- In essence, cancer is an uncontrollably growing cell disease that is frequently brought on by changes in the expression of genes related to DNA repair, apoptosis, cell cycle regulation, and other cellular functions.
GENE EXPRESSION
Genetic mutations that impair the regular operation of genes involved in cell division, growth, and proliferation give birth to cancer. These mutations can happen on their own or be brought on by a number of different things, like
being around radiation, infections, or toxins.
GENETIC MUTATIONS
Tumor suppressor genes control apoptosis, or programmed cell death, and prevent cell development, whereas oncogenes encourage cell division and
growth. One of the characteristics of cancer is unchecked cell proliferation,
which can be caused by mutations in oncogenes or by the inactivation of
tumor suppressor genes.
ONCOGENES AND TUMOR SUPPRESSOR GENES
Compared to normal cells, cancer cells frequently have aberrant patterns of
gene expression. This may entail the overexpression of oncogenes, which
promotes cell proliferation, or the underexpression of tumor suppressor
genes, which permits cancer cells to grow and survive unchecked.
ALTERATIONS IN GENE EXPRESSION
Cancer cells frequently experience epigenetic modifications, which modify
gene expression without changing the underlying DNA sequence, in addition
to genetic mutations. Histone modifications, DNA methylation, and changes in non-coding RNAs are examples of these modifications, which have the ability to mute tumor suppressor genes or activate oncogenes.
EPIGENETIC CHANGES
An essential part of the pathophysiology of cancer is the dysregulation of signaling pathways. Cancer cells may be encouraged to proliferate, survive, and undergo angiogenesis through the aberrant activation of growth factor
receptors, such as the EGFR or the PI3K/Akt/mTOR pathway.
SIGNALING PATHWAYS
Cancer cells’ patterns of gene expression are influenced by the extracellular matrix, immune cells, and stromal cells that surround them in the tumor microenvironment. Through alterations in gene expression, crosstalk between cancer cells and the surrounding tissue can stimulate tumor growth, invasion, and metastasis.
MICROENVIRONMENTAL FACTORS
a common mechanism used by cancer cells to maintain their fast growth and
division. Cancer cells are able to fulfill their increased energy demands
through a metabolic shift that involves changes in gene expression linked to
mitochondrial function, fatty acid synthesis, and glucose metabolism.
METABOLIC REPROGRAMMING
Therapeutic resistance in cancer cells can be attributed to changes in gene
expression, which reduces their responsiveness to immunotherapy, targeted therapies, or chemotherapy. Resistance mechanisms can include changes to DNA repair mechanisms, activation of survival pathways, or overexpression of drug efflux pumps.
THERAPEUTIC RESISTANCE
- medications that stop cancer cells from proliferating and spreading.
- function by going after cells that divide quickly, which is a hallmark of cancerous cells.
- Depending on the kind and stage of the cancer, chemotherapy may be used either alone or in conjunction with other treatments including immunotherapy, radiation therapy, or surgery.
CHEMOTHERAPEUTIC AGENTS
These drugs work by adding alkyl groups to DNA, which interferes with
DNA replication and ultimately leads to cell death. Common alkylating agents include:
- Cyclophosphamide - used to treat
breast cancer, lymphoma, and
leukemia. - Ifosfamide - used to treat testicular
cancer, ovarian cancer, soft tissue
sarcomas, and certain types of
leukemia. - Mechlorethamine - treatment of
Hodgkin’s lymphoma, non-Hodgkin’s
lymphoma, and certain types of
leukemia.
ALKYLATING AGENTS
Antimetabolites interfere with DNA synthesis by substituting for the natural building blocks of DNA or RNA.
- Methotrexate - used to treat leukemia,
lymphoma, and solid tumors - Fluorouracil (5-FU) - used to treat
colorectal cancer, breast cancer, and
cancers of the head, neck, and skin. - Cytarabine - used primarily in the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and non- Hodgkin’s lymphoma (NHL)
ANTIMETABOLITES
These drugs interfere with the action of topoisomerase enzymes, which are involved in DNA replication and repair.
- Etoposide - used to treat lung cancer,
testicular cancer, lymphoma, and leukemia. - Irinotecan - treatment of colorectal cancer and certain types of lung cancer.
- Topotecan - treatment of ovarian cancer, small cell lung cancer (SCLC), and cervical cancer.
TOPOISOMERASE INHIBITORS
