SMURF2 Inhibitors Increase Effectiveness of MEK Inhibitors

Treatments that target a protein called MEK could work better when combined with drugs that inhibit a protein called SMURF2, according to research in the British Journal of the National Cancer Institute. MEK is involved in cell division and can be activated by BRAF and NRAS mutations. However, melanomas often resist MEK inhibitors. The researchers found that MEK inhibitors made melanoma cells grown in the laboratory produce too much of a protein called SMURF2. This in turn led to overproduction of another protein called MITF, which protects melanomas against MEK inhibitors. When treated with both a MEK inhibitor called selumetinib and a SMURF2 inhibitor, tumor growth was suppressed by 98% in mice.

Primary source: http://jnci.oxfordjournals.org/content/105/1/33.abstract?sid=76bd523d-0853-4b55-abe1-b7781898c5a3


Cost-Benefit Analysis Questions Treating Medicaid Patients with Vemurafenib

The impressive, but still short-term, benefits of vemurafenib for melanoma patients may not justify the hefty cost to a Massachusetts Medicaid program, according to an analysis presented at an American Society of Health-System Pharmacists meeting. Vemurafenib targets the most common mutation of BRAF, which is one of the genes that is most often abnormal in melanomas. The analysis noted that vemurafenib boosted 6-month survival rates over those of the conventional chemotherapy drug dacarbazine (84% and 64%, respectively). However, vemurafenib is also more expensive than dacarbazine, with relative per patient costs estimated at $9,995 and $1,811 per month, respectively.


Treatment Breaks May Delay or Prevent Vemurafenib Resistance

Giving melanoma patients a break from vemurafenib could make this treatment more effective. Research in Nature shows that vemurafenib-resistant tumors keep growing during treatment because they produce high levels of mutated BRAF proteins, which are involved in cell division. Moreover, these tumors actually depend on the drug to grow. In contrast, an on-and-off treatment schedule can help keep melanomas from becoming resistant to vemurafenib in mice.

Primary source: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11814.html


Testing Lymph Nodes Near Melanomas May Not Help

A British Medical Journal report questions an invasive, expensive standard practice for melanoma patients in the U.S. Called sentinel node biopsy, the approach involves testing lymph nodes near tumors for cancer cells and removing nodes that test positive. The report cites a 2006 study showing that sentinel node biopsy did not increase 5-year survival rates and calls for further analysis of the practice’s effectiveness. Sentinel node biopsies are not standard in the UK.


Researchers Write New Guide to Optimal Treatments for Melanomas with BRAF Mutations

Based on current data, researchers have developed a new treatment guide for melanomas with the most common mutations (BRAF V600). While these melanomas can be targeted with vemurafenib and dabrafenib, challenges remain. Not all tumors respond, some become resistant, and side effects can include another type of skin cancer called squamous cell carcinoma. Other treatment options include trametinib, which targets a protein called MEK, as well as immunotherapies such as high-dose interleukin 2 and ipilimumab, both of which can control tumors completely.


Melanoma Apps No Substitute for Doctors

A JAMA Dermatology study shows the dangers of using smartphone apps to self-diagnose melanomas. The researchers compared diagnoses of 60 melanomas and 128 benign lesions by a board-certified dermatopathologist to those of four apps. Three of the apps incorrectly said that 30% or more of the melanomas were harmless. The fourth app, which sent images to board-certified dermatologists, was better, but still misdiagnosed one of the melanomas as benign. These apps are not subject to regulatory oversight.

Primary source: http://archderm.jamanetwork.com/article.aspx?articleid=1557488#qundefined


Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf


Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html


Study Suggests Iressa Effective for Elderly Patients with EGFR-Mutant Lung Cancer

A retrospective study in Japan examined 55 patients aged 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well tolerated and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.

Research paper: http://link.springer.com/article/10.1007/s12032-012-0450-2/fulltext.html