Cancer Research in Biotechnology Part II – Genetic Analysis

Gene expression profiling (GEP) is a powerful tool to identify genes and pathways that are abnormally expressed during carcinogenesis. While these discoveries enhance our understanding of molecular pathogenesis, they can also suggest novel therapeutic targets, provide information about drug resistance pathways, and refine prognostic classifications.

A major problem in clinical oncology is the heterogeneous response of histologically similar tumors to treatments such as cytotoxic chemotherapy. With the exception of estrogen/progesterone receptor, and HER2 (c-erbB-2) expression in breast cancer (for hormonal therapy and trastuzumab, respectively), EGFR kinase domain mutations and genomic amplification in lung cancer (in EGFR targeted inhibitors gefitinib or erlotinib), and K-ras mutations in colon cancer (lack of response to EGFR-targeted antagonists), there are no other single molecules that are clinically useful predictors of response validated for any form of anticancer therapy.

Encouraging emerging data suggest that prediction of response to chemotherapy or biologically targeted agents may be possible by analyzing gene expression profiles (GEPs). With rapid advances in the DNA microarray technologies and more sophisticated studies, microarray analysis has started to make ways into clinical trials and practices in oncology.

Several examples of the potential application of GEPs in clinical oncology are described here to illustrate the utility of this technology in common solid tumors and hematologic malignancies.

Acute leukemia – The first report to show that GEPs could be used to classify tumors analyzed a group of acute leukemias. Based upon gene expression patterns, acute myeloid leukemia (AML) could be distinguished from acute lymphoblastic leukemia (ALL) without standard histology information. Similarly, B-cell versus T-cell ALL could be separated based on GEP. This study served as proof of principle that clinically useful classifications could be made simply by gene expression patterns. In another report, a case with equivocal histology by standard criteria was accurately classified by gene analysis, demonstrating the potential utility of GEP beyond standard histologic and immunocytochemical methods.

Others have shown that GEP can distinguish among prognostically important subgroups of children with ALL and adults with AML, in some cases identifying those who eventually fail therapy. If these findings are confirmed by others, the logical next step is to apply a more intense initial treatment strategy to such patients, selected on the basis of their GEP.

It may also be possible to screen for agents capable of inducing leukemic cell differentiation through changes in their GEP. A major caveat is that gene expression profiles of clinical samples may differ significantly from those seen in cell lines representing the corresponding leukemia.

Prostate cancer – A potential application of GEP in men at risk for prostate cancer is the identification of biomarkers that can help select men with a borderline elevation in serum prostate specific antigen (PSA) for biopsy. In addition, GEP might be used to identify men whose early stage tumors are destined to recur and thus would benefit from more aggressive therapy.

GEP has been used to identify several genes (e.g., hepsin and pim-1) that are upregulated in prostate cancer compared to benign prostatic hyperplasia and normal prostate tissue, and some are highly correlated with clinical outcome [25-30]. Investigators have found a ≥3-fold difference in expression in over 3000 genes when nonrecurrent prostate cancers were compared to metastatic tumors.

Colon cancer – The serine phosphatase PRL-3 is consistently upregulated in metastatic as compared to non-metastatic colorectal cancers [31]. The finding that metastatic potential appears to be encoded in the primary has challenged the notion that metastases arise from rare cells that have acquired the ability to metastasize.

GEP is under study as a way to improve prognostication, and perhaps, individualize adjuvant therapy recommendations. An area of intense study is the use of GEP to predict which patients with node-negative resected colon cancer are at a relatively higher risk of relapse, and thus, might benefit from adjuvant chemotherapy, as is typically recommended for patients with node-positive disease.

Breast cancer – A molecular classification for breast cancer has been proposed based upon GEP. Luminal (mainly estrogen receptor [ER] positive), basal-like (mostly ER-negative), normal-like, and erbB2+ (mostly HER-2 overexpressing, ER-negative) subgroups have been identified, and have different prognoses.

A major area of investigation is the use of such molecular profiling to predict response to therapy. The GEPs of breast cancers that respond best to neoadjuvant (preoperative) chemotherapy (ie, basal-like, erbB2+) differ from those of nonresponding or resistant tumors.

Analysis of GEP can also distinguish sporadic breast cancers from those associated with BRCA mutations. Perhaps more importantly, GEP can also permit stratification of defined subgroups (ie, those with axillary lymph node-negative breast cancer or grade 2 tumors) into prognostically separate categories. In at least some reports, outcome prediction by GEP outperforms existing prognostic classifications. This topic is discussed in detail elsewhere.

GEP analysis by DNA microarray is available in patients with breast cancer (the 21-gene recurrence score assay, like Oncotype DX) to quantify the likelihood of a breast cancer recurrence in women with newly diagnosed, node-negative hormone receptor-positive early stage breast cancer. The assay is designed to identify those women whose risk of recurrence is low enough to justify the omission of chemotherapy and use of tamoxifen alone as systemic adjuvant therapy.

Although commercially available, the benefit of using 21-gene recurrence score assays (e.g, Oncotype DX) to select the adjuvant therapy strategy has not been tested in a prospective trial. Such an approach is being evaluated in the phase III Trial Assigning IndividuaLized Options for Treatment (Rx) (the TAILORx clinical trial), sponsored by the National Cancer Institute and led by the Eastern Cooperative Oncology Group (ECOG).

Radiation Oncology and Advancements in Cancer Research

As medical breakthroughs are discovered every day and preventions, cures and treatments become available for hundreds of diseases, cancer remains the number two cause of death for men and women in the United States behind heart disease.

This does not mean that cancer research is void of major breakthroughs or that it is not coming along as fast as advancements in other fields. It simply indicates that while new treatment technologies, such as radiation therapy are being developed and researched, they are not being accomplished at the same rate as diabetes, influenza, and cardiovascular disease treatment and preventions.

One of the problems with cancer treatment is that it is difficult to establish prevention techniques, to some degree. While doctors and scientists have learned that tobacco, asbestos, and other carcinogens can cause the disease; there are no strict guidelines that can guarantee a person will be free from cancer.

Some people have even argued that cancer is not a disease, but a “condition” and that, while avoiding tobacco and cancer causing agents can help, there is really nothing that can be done to reduce your chances of developing cancer beyond that.

Radiation Oncology — Advanced Treatments

Though the number of diagnosed cases of cancer may not be lowering quite as much as hoped, the number of deaths per diagnosed case has fallen dramatically in the past few years. As a matter of fact, cancer mortality rates have dropped dramatically since 1993, and a report by the New York Times states that in 2007, 12,000 fewer cancer patients died than did in 1993. Also stated in the article is that much of the progress comes from “early detection and treatment of some of the leading causes of cancer death — lung, colorectal, breast, and prostate tumors.”

One area in which the most improvement has come is radiation therapy. Radiation Therapy is — just as it seems it would be — the process of treating cancerous tumors via radiation. Radiation Oncology, the practice of physicians who use radiation therapy, involves dozens of different specialized treatment methods, which implement highly sophisticated technologies and equipment to deliver precise beams of radiation to the affected area without coming into contact with the surrounding tissues. An oncologist can use a multitude of specific therapy methods, only a couple of which are IMRT, or Intense Modulated Radiation Therapy, and TomoTherapy – each of which has its advantages and both of which are effective for issuing precise doses of radiation.

Only a radiation oncologist can help you decide exactly which form of radiation therapy might work best for a particular type of cancer, but overall advancements in oncology gives new hope to cancer patients across the world. As science continues to develop new tools and treatment methods, society can inch closer to a world that is cancer-free.

New Results in Cancer Research on Green Tea

Cancer as we know has been the most dreaded disease in the world. Statistics state that nearly 13% of the deaths occur worldwide because of cancer. The metastasis i.e. spread of mutated cells to other parts of the body occurs because of various reasons. They can b categorized as:

Physical: exposure to direct ultraviolet & other ionizing rays

Chemical: various impurities in water like arsenic & toxins like asbestos etc

Biological: certain bacterial & viral infection-mostly Human Papilloma Virus (HPV) can cause cancer

So where does drinking tea come in & why is it said to prevent risk from cancer?

Cancer research has been around for a long time as scientists try out their luck in finding a cure. And over the years green tea has become the top naturally available source which could hold a key to preventing if not curing cancer.

Green tea was first discovered in China from where its usage spread to other parts of Asia & then America. It was a preferred beverage because of its exotic taste & smell. Its medicinal properties came to light soon after & since then it has been attributed to being responsible in reducing weight, delaying ageing, decreasing risks of cancer & diabetes-type 2 etc. Research on cancer has found that the antioxidant property of green tea is perhaps the major deterrent to cancer.

Chinese green tea has been subjected to numerous researchs & studies, clinical trials carried out in vitro as well as on a group of people & have been found to be the most favourable in delaying and sometimes preventing cancer. The study found that the substance ECG-epigallocatechin gallate is a very strong antioxidant, which means its primarily responsible for flushing out toxins like arsenic & asbestos from the system.

Let’s take into consideration a Chinese research carried out by Mr.Zheng & his team. They used data from an older research carried out on 69,000 women. Although some 1200 of them did develop cancer, it was found that those who drank green tea on a regular basis had somewhat lower risks of getting the disease. Not only that, the women were also found running a 27% lower risk of getting digestive system cancer & 29% lower risk of colorectal cancer.

And when it comes to women, they run a high risk of breast cancer-which is the leading cause of deaths caused by cancer. In case of menopausal women such risk is greater. Breast cancer is caused when the female hormone oestrogen’s level increases after menopause. But when research was carried out on green tea drinkers, it was found that the oestrogen levels in their urine samples were quite less comparatively.

Green tea being a natural antioxidant & immunity enhancer is a great alternative to unhealthy fizzy drinks. Try this natural drink today & develop a taste for tea to stay healthy & live a long life!