Breast Cancer Gene Therapy

Name : Ch.Uha RekhaI.D Number : 2012510066

Gene Therapy• Definition : Gene therapy is a treatment that

involves altering the genes inside your body's cells to stop disease. Genes contain your DNA — the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your body's ability to fight disease.

Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis,

heart disease, diabetes, hemophilia and AIDS. In gene therapy, the nucleic acid molecule is

packaged within a "vector", which is used to get the molecule inside cells within the body. There are many techniques of gene therapy, all of them still in experimental stages. The two basic methods are called in vivo and ex vivo gene therapy. The in vivo method inserts genetically altered genes directly into the patient; the ex vivo method removes tissue from the patient, extracts the cells in question, and genetically alters them before returning them to the patient.

About The Disease• Breast Cancer : Breast cancer is a kind

of cancer that develops from breast cells. Breast cancer usually starts off in the inner lining of milk ducts or the lobules that supply them with milk. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, or a red scaly patch of skin.

Types Of Breast Cancer

A malignant tumor can spread to other parts of the body. A breast cancer that started off in the lobules is known as lobular carcinoma, while one that developed from the ducts is called ductal carcinoma. Cancer stem cells have recently been isolated from several different solid tumors. In breast cancer, the CD44+CD24−/low population is considered to comprise stem-like cells.

Identification of human primary breast cancer cells :

The purity of the primary mammospheres was verified by using flow cytometry and immunostaining. We found that no more than 0.5% of the primary mammospheres were positive for CD31 or CD45 by flow cytometry

• ReverTra Ace-α-1 (Toyobo, Osaka, Japan) was used

for semi-quantitative reverse transcriptase PCR (RT-PCR) with the following primers:

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sox2 reverse, 5 -GTGCTGGGACATGTGAAGTCT-3′ ;′• oct4 forward, 5 -CTCCTGAAGCAGAAGAGGATCAC-3′ ;′• oct4 reverse, 5 -CTTCTGGCGCCGGTTACAGAACCA-3′ ;′• β-actin forward, 5 -CATGTACGTTGCTATCCAGGC-3 ;′ ′• β-actin reverse, 5 -CTCCTTAATGTCACGCACGAT-3′ ′

Genomic Sequence of Breast Cancer :

•Breast cancer occurs due to changes in the DNA of breast tissue that cause certain cells to grow unchecked and form tumors. There are many different types of breast cancer and each one may have a different treatment and prognosis. According to a number of in-depth genetic analyses, the disease has been classified into four sub-types: 1.Luminal A 2.luminal B 3. HER2-positive4.Basal-like.

• Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific MOLECULES ("molecular targets") that are involved in the growth,PROGRESSION, and spread of cancer. Targeted cancer therapies are sometimes called "molecularly targeted drugs," "molecularly targeted therapies," "precision medicines," or similar names.

• Targeted therapies differ from standard chemotherapy in several ways:• Targeted therapies act on specific molecular targets that are associated with

cancer, whereas most standard chemotherapies act on all rapidly dividing normal and cancerous cells.

• Targeted therapies are deliberately chosen or designed to interact with their target, whereas many standard chemotherapies were identified because they kill cells.

• Targeted therapies are often cytostatic (that is, they block tumor cell proliferation), whereas standard chemotherapy agents are cytotoxic (that is, they kill tumor cells).

Targeted Cancer Therapies

The signs and symptoms of breast cancer :

• The first symptoms of breast cancer are usually an area of thickened tissue in the woman's breast, or a lump. The majority of lumps are not cancerous; however, women should get them checked by a health care professional. According to the National Health Service, UK, women who detect any of the following signs or symptoms should tell their doctor: 1. lump in a breast2.A pain in the armpits or breast that does not seem to be related to the woman's menstrual period.

• Pitting or redness of the skin of the breast; like the skin

of an orange• A rash around (or on) one of the nipples• A swelling (lump) in one of the armpits• An area of thickened tissue in a breast• One of the nipples has a discharge; sometimes it may

contain blood• The nipple changes in appearance; it may become

sunken or inverted• The size or the shape of the breast changes• The nipple-skin or breast-skin may have started to peel,

scale or flake.

The causes of breast cancer• It is hard to say why one person develops the disease

while another does not. We know that some risk factors can impact on a woman's likelihood of developing breast cancer.

Getting older - the older a woman gets, the higher is her risk of developing breast cancer; age is a risk factor. Over 80% of all female breast cancers occur among women aged 50+ years (after the menopause).

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Genetics - women who have a close relative who has/had breast or ovarian cancer are more likely to develop breast cancer. If two close family members develop the disease, it does not necessarily mean they shared the genes that make them more vulnerable, because breast cancer is a relatively common cancer.

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The majority of breast cancers are not hereditary•

• A history of breast cancer - women who have had breast cancer, even non-invasive cancer, are more

likely to develop the disease again, compared to women who have no history of the disease.•

Having had certain types of breast lumps - women who have had some types of benign (non-cancerous)breast lumps are more likely to develop cancer later on. Examples include atypical ductal hyperplasia or lobular carcinoma in situ.

•Dense breast tissue - women with more dense breast tissue have a greater chance of developing breast cancer.

•Estrogen exposure - women who started having periods earlier or entered menopause later than usual have a higher risk of developing breast cancer. This is because their bodies have been exposed toestrogen for longer. Estrogen exposure begins when periods start, and drops dramatically during the menopause.

•Obesity - post-menopausal obese and overweight women may have a higher risk of developing breast cancer. Experts say that there are higher levels of estrogen in obese menopausal women, which may be the cause of the higher risk.

•Height - taller-than-average women have a slightly greater likelihood of developing breast cancer than shorter-than-average women. Experts are not sure why.

Diagnosing breast cancer

• Women are usually diagnosed with breast cancer after a routine breast cancer screening, or after detecting certain signs and symptoms and seeing their doctor about them.

Breast exam - the physician will check both the patient's breasts, looking out for lumps and other possible abnormalities, X-ray (mammogram) - commonly used for breast cancer screening. If anything unusual is found, the doctor may order a diagnostic mammogram.

• 2D combined with 3D mammograms - 3D mammograms, when used in collaboration with regular 2D mammograms were found to reduce the incidence of false positives, researchers from the University of Sydney's School of Public Health, Australia, reported in The Lancet Oncology. Breast ultrasound - this type of scan may help doctors decide whether a lump or abnormality is a solid mass or a fluid-filled cyst

• Biopsy - a sample of tissue from an apparent abnormality, such as a lump, is surgically removed and sent to the lab for analysis. It the cells are found to be cancerous, the lab will also determine what type of breast cancer it is, and the grade of cancer (aggressiveness) Breast MRI (magnetic resonance imaging) scan - a dye is injected into the patient. This type of scan helps the doctor determine the extent of the cancer.

Gene therapy for breast cancer

• Gene therapy for advanced breast cancer is anticipated to be a useful therapeutic approach. Strategies in ongoing clinical protocols can be divided into four groups: (1) suppression of oncogenes or transfer of tumor-suppressor genes; (2) enhancement of immunological response; (3) transfer of suicide genes; (4) protection of bone marrow using drug resistance genes.

Micrograph showing a lymph node invaded by ductal breast carcinoma, with extension of the tumour beyond the lymph node.

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