Dear colleagues..
We are trying to find the essential genes or proteins that promote chemotherapy resistant in cancer in order to identify them in our study. Does anyone can suggest some?
Thank you a head.
Oncogenes are genetic mutations that result in uncontrolled cell growth, potentially leading to the development of cancer. Proto-oncogenes, on the other hand, are typically healthy genes that regulate and maintain proper cell growth. However, when proto-oncogenes undergo mutations, they can transform into oncogenes, thereby disrupting normal cellular processes and promoting cancer formation.
Hello Hamad Ali Hamad
I would suggest a few which you could include in your study.
Multidrug resistance of cancer cells during chemotherapy can be associated with a variety of mechanisms, including enhanced efflux of drugs, genetic factors (gene mutations, amplifications, and epigenetic alterations), growth factors, increased DNA repair capacity, and elevated metabolism of xenobiotics.
Transmembrane transporters responsible for the drug efflux are primarily from the ABC transporter superfamily. The human genome contains 48 ABC genes, and they are classified into seven subfamilies (ABCA-ABCG). Among them, ABCB1, ABCC1 and ABCG2 are highly involved in the acquisition of multidrug resistance to cancer chemotherapeutics.
Losing the tumor-suppressive activities by missense mutations in the TP53 gene, which are especially widespread in human cancers, reverses the protective role of the TP53 pathway by initiating chemoresistance, invasion, and metastasis. Loss of the TP53 activity in cancer cells allows continued replication no matter the type/level of DNA damage, which makes them resistant to genotoxic drugs.
Mutation in gene encoding enzymes involved in DNA damage response (DDR) such as ataxia telangiectasia (ATM), ATR, RAD50, and WRN can enhance the risk of cancer emergence and resistance. Single nucleotide polymorphisms in DNA repair-associated genes can also induce cancer drug resistance.
Focal adhesion kinase (FAK), a tyrosine kinase also referred as PTK2 (non-receptor protein tyrosine kinase) is a downstream protein of integrin and growth factor receptors signaling pathways. FAK induces NF-κB pathway mediated cytokine production in response to DNA damage. This phenomenon protects the cells from DNA damage and maintains chemo-resistance in the cells.
The cancer cells can cause drug resistance via providing multiple copies of the dihydrofolate reductase gene. The gene amplification increases the copy numbers of the oncogenes per cell to several hundred folds.
Transcription factors superfamily comprising DNA binding domain includes Forkhead box (FOX) proteins. FOX has been reported to regulate cellular machinery and various homeostatic processes. FOX factors control numerous physiological processes including cell division, cell death, cell invasion and migration as well as drug resistance. Deregulation of FOX proteins is commonly associated with cancer initiation, progression, and chemotherapeutic drug resistance in many human tumors.
For more, you would want to refer to the articles attached below.
https://cdrjournal.com/article/view/3039
https://cdrjournal.com/article/view/3056
Best.
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