MOLECULAR BASIS OF CANCER

GUIDE FOR LAB CLASSES

This guide contains the links to help you to explore basics questions related with the molecular basis of Cancer and different Therapy approaches.

1. 1)BASIC INFORMATION OF CANCER
   

2. -NATIONAL CANCER INSTITUTE (NCI): Go to Cancer type and Check for Breast cancer [B] (Health Professional Version). Then go to Treatment and read through
   

the different pages of Treatment Options until drugs approved for Breast Cancer.

Check also Causes and Statistics

- Cancer genes, classified by Theme or by Cell Biology:

ATLAS OF GENETICS AND CYTOGENETICS IN ONCOLOGY AND HEMATOLOGY

CANCER GENES: Search for: e.g. RB1 (Retinoblastoma), Tp53 (Li-Fraumeni syndrome) and Her2 (ERBB2)

CELL/MOLECULAR BIOLOGY: Check by cell biology classification; e.g. apoptosis

- Pathways for a specific biological processes:

Pathways: Biocarta >Check Cell Cycle: G1/S Check Point

2) MUTATIONS AND CANCER

1. -THE CANCER GENOME PROJECT (SANGER INSTITUTE)-
   

Go to Resources and select:

CANCER GENE CENSUS: Breakdown: Check for genes with gene amplification and also: Nonsense mutation within the BRCA1 gene

COSMIC 3D: A Platform for understanding cancer mutations in the context of 3D protein structure. Check for MDM2

GENOMICS OF DRUG SENSITIVITY IN CANCER; 

Compounds: Etoposide. See Overview, cell lines ranked by drug sensitivity, genes mutated and effect

Also Look by Genes (cancer features), e.g. KRAS

and by Cell Line, e.g. HCT-116

3) PHARMACOGENOMICS IN CANCER

1. -CANCER GENOME ANATOMY PROJECT (CGAP) e.g. RNA-interference constructs, targeted specifically against cancer relevant genes (shRNA library). Search for Bcl2
   

1. -THE CANCER GENOME ATLAS (TCGA) Understanding Genomics to improve Cancer care.
   

2. -Launch Data Portal to get an array of array-data: Choose breast cancer as an example (Breast invasive carcinoma) (TCGA-BRCA)--Check for most frequently mutated genes.
   

1. -The cBioPortal for Cancer Genomics: provides visualization, analysis and download of large-scale cancer genomics data sets.  Select Colorectal adenocarcinoma  > View Summary > Query KRAS > Check for expression, and Mutations
   

1. -Also, select UCSC Cancer Genomics Browser. Go to Cancer Browser and then add a dataset, e.g. breast invasive cancer (Gene expression arrays- Agilent).
   

2. -See the heatmap representation for Chromosomes;  and then for Genes: go to advance genes and select PAM50 (Gene expression signature)
   

signature and also look for individual genes: e.g. ERBB2.

1. -GENE EXPRESSION OMNIBUS (Check for microarray analysis results of cancer experiments). Go to Datasets. Look for “Breast cancer versus normal epithelial” , then use GSE series GSE10797
   

2. -Analyze with GEO2R
   

4) CANCER THERAPEUTICS

- DEVELOPMENTAL THERAPEUTICAL PROGRAM NCI/NIH

NCI-60: Check the cell lines used in the screen to test the effect of new drugs in Drug Discovery and Development Services: List of the NCI-60 Human Tumor Cell Lines

1. -Compare the effect of different drugs, like a BLAST of Drugs
   

2. -DTP-Data Search: Search for a drug name (search for all data of compounds within “Search DTP Screening Data”): e.g. Methotrexate
   

and Get a NSC number (NSC 740)

DTP-COMPARE: Check Methotrexate (using its NSC). Then select an Open Data experiment and GI50 (Growth Inhibitory 50) values and Run Standard Compare.

Give a name at “Lookup Word” for instance your last name.

Manage jobs. Enter the “lookup word” and Retrieve the COMPARE results

(by fetching standard compare jobs) You must select “complete-select this job”.

Get the ranked list of all the compounds with the similarity at the level of GI50

between the seeded drug and the correlated drugs.

1. -Anticancer Agents - My Cancer Genome This is a list by groups of the different anticancer agents
   

1. -SIDER 4, Side Effect Resource
   

5) PHARMACOGENETICS OF CANCER

1. -dbSNP
   

1. -SNPs3D
   

- PharmGKB: (The Pharmacogenetic and pharmacogenomic knowledge database)

Look for Imatinib (Gleevec) and Irinotecan: pathways, mechanisms of action; and resistance. Also find information for the following genes related to cancer therapy within the same web:

1. -TPMT: Thiopurine methyl transferase (In immunodeficiencies treated with AZA or 6-MP)
   

2. -UGT: Uridine diphosphateglucuronidil transferase (Gilbert Syndrome upon Irinotecan)
   

3. -MDR1 (Multi drug resistance transporter)
   

4. -DPD (dihydropyrimidine dehydrogenase) 5-Fluorouracil toxicity.