Cancer is a heterogeneous disease. Above all, therapeutic success in unpredictable.
Its result from inflammation...caused by perturbed proteases and kinases, wrecking havoc with normal functionality of body. Pesticides and household endocrine disruptors are increasing risks of cancer.
Personalized medicine is required to treat it, as genetics of each individual is different.
Poor prognosis, metastasis, high relapse rate make cancer deadly
Mapping the mutations, genes and their pathways can reveal a lot about cancer.
Diagnosis: Ultrasound, colonoscopy, mammography..
Current therapeutic strategy include: surgery (mastectomies), chemo, radiotherapy, molecular targeted therapy
TCGA: Cancer Genome Atlas consortium
MURINE......
26L5: murine colon carcinoma
B16BL6: murine melanoma,
murine Lewis lung carcinoma
HUMAN....
A375 : human melanoma
A498: Renal carcinoma
A549: human lung adenocarcinoma
AMC-HN-4: malignant human head and neck
BT474: human breast
ChaGo: human bronchogenic
CNE1: nasopharyngeal carcinoma
DU145: hormone-resistant prostate cancer
GBM : human glioblastoma
HCC: Hepatocellular carcinoma
HeLa: human cervix adenocarcinoma
Hep-G2:human liver
HT-1080: humanfibrosarcoma
KATO-III: human gastric
LNCaP: hormone-sensitive prostate cancer
MCF-7: human breast cancer ERα+
mCRPC: metastatic castration resistant prostate cancer
PBMC: human peripheral blood mononuclear cell
PC-3: human colon carcinoma
SW620: human colon
U87MG: human glioblastoma
Normal cell lines (control)
CH-liver
HCT116
HS27: fibroblast
HT29
SW480 cells
Human genes associated with different cancers/cancer-associated genes:
There are 20K genes in humans, out of which some are constantly linked to diseases
Colon: BCL9L, RBM10, CTCF, and KLF5
Cervical adenocarcinoma:
Breast cancer: BRCA1 and BRCA2
Ovarian cancer. BRCA1 and BRCA2
HER2 gene (human epidermal growth factor receptor 2; receptor tyrosine-protein kinase erbB-2, also known as CD340, proto-oncogene Neu, Erbb2, or ERBB2, is a protein-coding gene) amplification is associate with breast, stomach, esophagus cancers
(> 6 copies of the HER2 gene has been found)
Amplification (extra copies) of HER2 can drive tumor growth by promoting cell division, cell longevity, and formation of new blood vessels.
HER2 gene amplification is now considered a “druggable target”
So, same drugs and same laboratory testing methods can be used
Testing should begin at the protein level with analysis of the HER2 receptor drug target on the surface of the tumor cells
Then the HER2 gene copy number on chromosome 17 is tested for amplification
HER2 protein has TryKc and FU domain. The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation
MET
MET exon 14 mutations are seen in NSCLC/Non–small-cell lung cancers
Patients whose cancers have MET exon 14 skipping (a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections of genetic code, leading to a truncated but still functional protein despite the genetic mutation)can respond well to MET inhibitors
genomic mutations and copy number alterations
c-Met tyrosine kinase dysregulation can be due to overexpression, gene amplification, mutation, a ligand-dependent auto- or paracrine loop or an untimely activation of receptor tyrosine kinases
HGF is the natural high-affinity ligand for Met
TP53
Deletion (loss of one or both copies) of tumor protein 53 (TP53) or other tumor suppressors, makes normal cells vulnerable to DNA replication errors. Cells that cannot repair or eliminate defective DNA are launched on a path towards cancer.
----------------
Lung Cancer-associated genes
AKT1
ALK
BRAF
CD274
DDR2
EGFR
ERBB2
FGFR1
FGFR3
KRAS
MAP2K1
MET
NRAS
NTRK1
PIK3CA
PTEN
RET
RICTOR
ROS1
Its result from inflammation...caused by perturbed proteases and kinases, wrecking havoc with normal functionality of body. Pesticides and household endocrine disruptors are increasing risks of cancer.
Personalized medicine is required to treat it, as genetics of each individual is different.
Poor prognosis, metastasis, high relapse rate make cancer deadly
Mapping the mutations, genes and their pathways can reveal a lot about cancer.
Diagnosis: Ultrasound, colonoscopy, mammography..
Current therapeutic strategy include: surgery (mastectomies), chemo, radiotherapy, molecular targeted therapy
TCGA: Cancer Genome Atlas consortium
MURINE......
26L5: murine colon carcinoma
B16BL6: murine melanoma,
murine Lewis lung carcinoma
HUMAN....
A375 : human melanoma
A498: Renal carcinoma
A549: human lung adenocarcinoma
AMC-HN-4: malignant human head and neck
BT474: human breast
ChaGo: human bronchogenic
CNE1: nasopharyngeal carcinoma
DU145: hormone-resistant prostate cancer
GBM : human glioblastoma
HCC: Hepatocellular carcinoma
HeLa: human cervix adenocarcinoma
Hep-G2:human liver
HT-1080: humanfibrosarcoma
KATO-III: human gastric
LNCaP: hormone-sensitive prostate cancer
MCF-7: human breast cancer ERα+
mCRPC: metastatic castration resistant prostate cancer
PBMC: human peripheral blood mononuclear cell
PC-3: human colon carcinoma
SW620: human colon
U87MG: human glioblastoma
Normal cell lines (control)
CH-liver
HCT116
HS27: fibroblast
HT29
SW480 cells
Infection of B cells with Epstein-Barr virus (EBV) leads to proliferation and subsequent immortalization, resulting in establishment of lymphoblastoid cell lines (LCL) in vitro. Since LCL are latently infected with EBV, they provide a model system to investigate EBV latency and virus-driven B cell proliferation and tumorigenesis
Human genes associated with different cancers/cancer-associated genes:
There are 20K genes in humans, out of which some are constantly linked to diseases
Colon: BCL9L, RBM10, CTCF, and KLF5
Cervical adenocarcinoma:
Breast cancer: BRCA1 and BRCA2
Ovarian cancer. BRCA1 and BRCA2
HER2 gene (human epidermal growth factor receptor 2; receptor tyrosine-protein kinase erbB-2, also known as CD340, proto-oncogene Neu, Erbb2, or ERBB2, is a protein-coding gene) amplification is associate with breast, stomach, esophagus cancers
(> 6 copies of the HER2 gene has been found)
Amplification (extra copies) of HER2 can drive tumor growth by promoting cell division, cell longevity, and formation of new blood vessels.
HER2 gene amplification is now considered a “druggable target”
So, same drugs and same laboratory testing methods can be used
Testing should begin at the protein level with analysis of the HER2 receptor drug target on the surface of the tumor cells
Then the HER2 gene copy number on chromosome 17 is tested for amplification
HER2 protein has TryKc and FU domain. The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation
MET
MET exon 14 mutations are seen in NSCLC/Non–small-cell lung cancers
Patients whose cancers have MET exon 14 skipping (a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections of genetic code, leading to a truncated but still functional protein despite the genetic mutation)can respond well to MET inhibitors
genomic mutations and copy number alterations
c-Met tyrosine kinase dysregulation can be due to overexpression, gene amplification, mutation, a ligand-dependent auto- or paracrine loop or an untimely activation of receptor tyrosine kinases
HGF is the natural high-affinity ligand for Met
TP53
Deletion (loss of one or both copies) of tumor protein 53 (TP53) or other tumor suppressors, makes normal cells vulnerable to DNA replication errors. Cells that cannot repair or eliminate defective DNA are launched on a path towards cancer.
----------------
Lung Cancer-associated genes
AKT1
ALK
BRAF
CD274
DDR2
EGFR
ERBB2
FGFR1
FGFR3
KRAS
MAP2K1
MET
NRAS
NTRK1
PIK3CA
PTEN
RET
RICTOR
ROS1
Well-known cancer pathways
Wnt pathway
Canonical
Wnt binds to its receptor Frizzled, and potential co-receptor LRP-5/6
It suppresses GSK-3ß phosphorylation of ß-Catenin.
ß-Catenin accumulates in nucleus
it binds to LEF/TCF transcription factors, which activate Wnt target genes.
Non-canonical
Wnt binds to Dishevelled protein by tyrosine kinase
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