Incoming and Outgoing Shipments in 1 STEP Using Odoo 17
CHEM1110 Chemistry For The Life Sciences I.docx
1. CHEM1110 Chemistry For The Life Sciences I
Answers:
Introduction
Regulation of the cells' proliferation is fundamental in maintaining genome integrity to
prevent cancer development. Cell division is initiated by extracellular growth factors
including the receptors, intracellular signals and nuclear transcription factors. Epidermal
Growth Factor Receptor (EGFR) is a crucial paradigm that reveals the signal from the
extracellular growth factor to initiate transduction and monitor gene expression that
regulates cellular proliferation. The receptor tyrosine kinase family includes the ErbB2,
ErbB3 and ErbB4, which essentially have the transmembrane domain, cytoplasmic tyrosine
kinase domain, and ligand-binding domain (Pecorino, 2021). Signaling for gene expression
involves ligand binding to growth factor, dimerization, autophosphorylation then activation
of the intracellular transducer. Various domains are recruited in signaling, such as the Src
Homology domains with a different number of amino acids within the EGFR cascade. Once
the EGF binds to the receptors, there is a change in the shape which enables two receptors
to merge; GRB and SOS proteins are recruited towards the membrane (Pecorino,
2021). RAS is activated by SOS hence inducing the RAF signal transducer. RAS 2 proteins,
RAF 3 and Mitogen-activated Protein Kinases (MAPK) are essential in cellular growth
regulation within the EGFR pathway utilizing different domains.
Fig. 1 Showing the EGFR cascade (Pecorino, 2021).
RAS Proteins
RAS proteins are essential contributors to the regulation of the EGFR transduction
pathway. The proteins build the point of integrating cellular growth signals inducing the
signaling cascade from the cell membrane to the nucleus via the cytoplasm. Members
within this domain are K-RAS, N- and H-. RAS act as binding sites allowing the GDP; when
bound to GDP, they become active (Pecorino, 2021). The proteins are essential because
they possess a self-regulation mechanism that controls the GTPase activity. Nucleotide
exchange factors initiate the catalysis of GDP to GTP, which will terminate the EGFR
2. cascade; thus, RAS controls the activity. EGFR pathway involves interactions of proteins
facilitated by SH3 domains of Grb2 and SOS, which targets the RAS (Pecorino, 2021). The
domain is responsible for trafficking within the cell and conducts farnesylation. Notably,
RAS proteins activate signaling pathways, especially in cell proliferation, differentiation, or
apoptosis. The protein domain transforms cells from the cellular compartments and
membrane while RAS adheres to cellular signals for growth regulation within the EGFR
pathway that can be used to develop new tumor treatments.
Fig. 2: Showing the EGF pathway (Pecorino, 2021).
RAF Proteins
Rapidly Accelerated Fibrosarcoma possesses serine/threonine activity that is important in
activating the EGFR pathway. The proteins are responsible for tumorigenesis through
regulating cell proliferation, metabolism and apoptosis (Pecorino, 2021). The activated RAF
conveys the signal from the membrane in the EGFR pathway. RAF has a recognized effector
that activates the RAS-GTP. The domain is responsible for transduction signals from the
extracellular to the intracellular compartment, where growth factors are activated and cell
growth initiated within the nucleus. Cell cycle progression and cellular docking are other
fundamental roles of the RAF domain during the EGFR cascade. Non-enzymatic roles must
act as transcription factors and initiate biological responses (Pecorino, 2021). RAF is
involved in cancer therapy development by determining the growth of upstream
factors. EGFR is critical in determining the origin of tumors or the uncontrollable behaviour
of human epithelial cells. RAF proteins activate the ERK cascade for cellular migration, and
its dependence on cancer therapies is developed.
MAP Kinase Cascade
Mitogen-activated protein kinase is essential in providing the cytoplasmic link for the
activated RAS and controls the gene expression. Different pathway mechanisms exist, and
the domain activates the environmental stress signals. The protein kinase is necessary for
directing cellular responses such as osmotic stress or mitogens. The MAP kinase proteins
act as antineoplastic agents tied to the EGFR pathway. The family classes of the MAPK
family include the extracellular signal-regulated kinases, JNKs or p38s, which the cells are
facilitated to mediate with the growth factors (Pecorino, 2021). The domain responds to
enzymes activity and regulates the substrates, DNA stability or gene
expression. Phosphorylation within the EGFR pathway controls the action of the
actions. Dysregulation of the MAPK domain reveals the induction or treatment of
cancer. The proteins are involved in conducting the transcription physiology of the genes
within the EGFR pathway (Pecorino, 2021). The domain remains critical in targeting cancer
therapeutics. The ability of the MAPK cascade to transmit signals is essential to modulate
the transcription suppressors or factors and attain a safe cellular response.
3. EGFR Targeted Medications
Understanding the EGFR transduction pathway is essential in launching new cancer
regimes. Most kinases have been designed as the targeted therapeutics for tumor
management. Some of the approved medications for cancer utilizing the EGFR cascade
concept include the anti-EGFR drugs for breast cancer patients. Common drugs include
Tarceva, gefitinib and Tykerb, which inhibit the tyrosine kinase activity (Pecorino,
2021). Monoclonal antibodies are also used to target the extracellular domain and include
Herceptin, approved in 1998 by FDA, which decreases angiogenesis. Erbitux and Vectibix
are also other monoclonal drugs targeting the EGFR pathway; they can reveal the oncogenic
signals. Physicians use pharmacogenomics to determine the drug of choice for different
cancers. Nexavar is a multi-kinase inhibitor that targets the RAF binding site in treating
hepatocarcinoma (Pecorino, 2021). Although it has shown resistance, Vemurafenib is an
RAF inhibitor approved to treat melanoma and results in tumor regression. Patients with
mutations of the RAS or RAF genes are prescribed MEK inhibitors such as the Imatinib used
to treat chronic myelogenous leukemia. The molecular biology understanding of the EGFR
cascade improves the targeting and development of appropriate cancer medications that
improves the drug's efficacy.
Conclusion
Cancer is a devastating phenomenon in the world today that demands attention. EGFR
family in adherence to the domains of proteins are used in diagnosis as biomarkers/
treatment regimes. Utilization of RAS, RAF and the MAPK cascades improves the
therapeutic goals for cancer treatment. The domains aim at inducing an anti-proliferation
mechanism and involve monoclonal or tyrosine kinase inhibitors. Some of the approved
medications that target the sites within the cell with the protein domains include Erbitux,
Vemurafenib, Imatinib and gefitinib.
Reference
Pecorino, L. (2021). Molecular biology of cancer: mechanisms, targets, and
therapeutics. Oxford university press.