New Evidence For The Genetic Bases Of Liver Cancer

Main Category: Liver Disease / Hepatitis
Also Included In: Cancer / Oncology;??Genetics
Article Date: 03 Jul 2013 - 1:00 PDT Current ratings for:
New Evidence For The Genetic Bases Of Liver Cancer

The Asian Cancer Research Group (ACRG), an independent, not-for-profit company in collaboration with BGI, the world's largest genomics organization, and The University of Hong Kong (HKU), jointly announced the publication of findings from a study of recurrent mutations in hepatocellular carcinoma (HCC), one of the most deadly cancers worldwide, in the international journal Genome Research . The study provides new insights into potential therapeutic intervention strategies for this common form of liver cancer.

HCC is a primary malignancy of the hepatocytes, generally leading to death within 6-20 months after diagnosis. This type of cancer is more common in parts of Africa and Asia, where the patients with hepatitis B or C are at risk for liver cancer, even if they have not developed cirrhosis. HCC has limited treatment options such as surgical resection of the tumor at its early stage, and the molecular basis of its occurrence and development remains poorly understood.

In this study, researchers used whole genome sequencing (WGS) to survey a cohort of 88 matched HCC tumor and normal samples from Hong Kong for investigating alerted genes and the pathways implicated in HBV-associated HCC. They found that TP53 was the most commonly mutated tumor suppressor gene, accounting for 35.2% in the HCC cohort. Generally, the patients with tumors containing TP53 mutations exhibited poor survival.

The Wnt/β-Catenin signaling pathway is central for liver functions and is frequently abnormal activated in the carcinogenesis of HCC. Researchers in this study found β-catenin maybe the most frequently mutated oncogene. In addition to β-catenin, they found relative high mutation rates in genes in the JAK/STAT pathway, which may act as a major oncogenic driver in HCC tumor progression.

Hancheng Zheng, group leader of this project at BGI, said, "Liver cancer is intractable to nearly all currently available anti-cancer targeted therapies. Our findings in this study provide a better understanding of molecular basis of hepatocarcinogenesis and provide new clues to improving the diagnosis and treatment of liver cancer in the future."

"We detected a series of genes and pathways implicated in HBV-associated HCC using whole genome sequencing, which contribute to a better understanding of the tumor biology and targeted drug screening," said Dr. James Hardwick, Vice President of ACRG, and Director of Informatics & Analysis at Merck, "The ACRG was established to fuel research directed towards improving our understanding of cancers affecting Asian populations. By working together, we are able to generate important breakthroughs that can be transformed to better fight against liver cancer in the future."

"As clinicians, we are very excited about the several prevalent and actionable mutations identified from the study, including activating mutations of JAK1, which warrant testing several existing inhibitors for the treatment of the disease preclinically and clinically," said Dr. Ronnie Poon, Chair Professor and Chief, Division of Hepatobiliary and Pancreatic Surgery, The University of Hong Kong.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Additional Evidence That Post-Lumpectomy Radiation Improves Breast Cancer Outcomes

?In addition to reducing the risk of breast cancer recurrence, post-lumpectomy radiation therapy improves survival among women with early breast cancer. These results—from a combined analysis of 17 previous studies—were published in The Lancet.?????

Surgery for early-stage breast cancer may consist of mastectomy or lumpectomy. A?mastectomy?involves removal of the entire breast, whereas a?lumpectomy?involves removal of the cancer and some surrounding tissue. A lumpectomy is usually followed by radiation therapy in order to reduce the risk of cancer recurrence in or near the breast. The combination of lumpectomy and radiation therapy is referred to as breast-conserving therapy.???

Several previous studies have reported giving radiation therapy after lumpectomy results in a lower risk of breast cancer recurrence than lumpectomy alone. To further evaluate the benefits of post-lumpectomy radiation therapy, researchers conducted a combined analysis of 17 previous studies. These studies included more than 10,000 women with early-stage breast cancer.???

Post-lumpectomy radiation therapy reduced the 10-year risk of breast cancer recurrence from 35% to 19%. ?The 15-year risk of death from breast cancer was 25% among women who did not receive post-lumpectomy radiation therapy and 21% among women who did receive radiation therapy. ?For every four breast cancer recurrences that were prevented by radiation therapy by year 10, one breast cancer death was prevented by year 15.?Benefits of radiation therapy were seen in women with node-negative breast cancer as well as women with node-positive breast cancer.?

These results provide additional evidence that giving radiation therapy after a lumpectomy substantially reduces the risk of cancer recurrence and also reduces the risk of death from breast cancer.?????

Reference: Early Breast Cancer Trialists’ Collaborative Group. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. Early online publication October 20, 2011.?

Posted October 27, 2011?

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Some Evidence of Mild “Chemo Brain” in Breast Cancer Survivors

Breast cancer patients treated with chemotherapy are at risk for mild cognitive deficits (sometimes referred to as chemo brain) after treatment, according to the results of a study published early online in the Journal of Clinical Oncology. ?

A large portion of breast cancer patients will ultimately receive adjuvant chemotherapy. Patients undergoing chemotherapy have long complained of a phenomenon referred to as “chemo brain.” Chemo brain refers to changes in cognitive function, such as loss of memory and inability to think clearly or perform some daily functions. Thus far, researchers have not been able to pinpoint the cause of chemo brain, but studies are ongoing to evaluate brain structure and function in order to better understand the effects of chemotherapy on the brain.?

There is mixed evidence regarding the scope and duration of chemo brain. Many studies have not focused on the post-chemotherapy period and thus have produced little data regarding the long-term effects of chemotherapy on the brain. ?

Researchers from the Moffitt Cancer Center conducted a meta-analysis of 17 studies that included 807 patients previously treated with standard-dose chemotherapy for breast cancer. The goal was to evaluate cognitive functioning in breast cancer survivors more than six months after being treated with chemotherapy. The studies included neuropsychological tests categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.?

The results of the analysis indicated that patients treated with chemotherapy had mild impairments in verbal ability and visuospatial ability compared to non-cancer controls. Cognitive impairment varied across survivors; however, the researchers reported that age, education, time since treatment, and hormonal therapy did not seem to have an effect on the observed cognitive deficits. ?

The researchers concluded that, on average, cognitive deficits in breast cancer patients who were previously treated with chemotherapy are mild and are limited to verbal and visuospatial abilities. They suggest that this information can be used to educate patients regarding the long-term impact of chemotherapy so that patients can develop interventions and modifications to cope with cognitive effects. Breast cancer patients who experience cognitive deficits may need to visit a neuropsychologist for evaluation and coping strategies. ?

Reference:?

Jim HSL, Phillips KM, Chait S, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. ?

Posted September 17, 2012

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