New Treatment Offers Mesothelioma Patients Hope

Last month, the U.S. Food & Drug Administration (FDA) approved the NovoTTF-100L system, a new first-line therapy for treating malignant pleural mesothelioma. This is the first treatment for mesothelioma to receive approval in over 15 years. NovoTTF-100L uses Tumor Treating Fields, a type of therapy that emits electric currents to disrupt cancer cell division and tumor growth.

NovoTTF-100L was created by Novocure and approved under the FDA’s Humanitarian Device Exemption eight months after Novocure released results from the STELLAR phase 2 clinical trial. The STELLAR trial was carried out at cancer centers across Europe and included 80 patients with unresectable, previously untreated malignant pleural mesothelioma. Results in the trial showed that patients treated with NovoTTF-100L survived six months longer, on average, than patients receiving only chemotherapy. There were  no reported major side effects or system toxicities, although 46 percent of patients noted skin irritation from using the device, but only 4 percent reported grade 3 skin irritation.

Ninety-seven percent of patients saw a clinical benefit from using the system, including either a partial response or stable disease. The median overall survival for patients with epithelioid mesothelioma – the most common cell type – was 21.2 months. Patients with sarcomatoid or biphasic cell types survived 12.1 months on average. Patients in the Tumor Treating Fields group saw a progression-free survival of 7.6 months, compared to 5.7 months for the chemotherapy group only.

The FDA approved the Tumor Treating Fields delivery system for use in combination with pemetrexed and platinum-based chemotherapy for unresectable, locally advanced or metastatic malignant pleural mesothelioma. NovoTTF-100L uses low-intensity alternating electric fields, which are calibrated to interfere with the division of cancer cells. For mesothelioma patients, the currents are delivered noninvasively to the upper torso and the system is intended for home use.

This is an important breakthrough for mesothelioma patients, as only 10 to 20 percent of patients qualify for tumor reduction surgery, according to In 2011, the FDA approved Optune, another Tumor Treating Fields device, for the treatment of glioblastomas.

Vitamin D Helps Slow Colorectal Cancer Progression

Results from the SUNSHINE trial by researchers at the Dana-Farber Cancer Institute suggest that supplementing chemotherapy treatments with high doses of vitamin D may help delay the progression of metastatic colorectal cancer. The study’s initial findings were reported at the 2017 American Society of Clinical Oncology meeting and have since been published in JAMA. A larger trial at hundreds of sites across the United States is set to begin later this year.

The SUNSHINE trial tested the effects of different doses of vitamin D in 139 patients being treated with chemotherapy for colorectal cancer. One group of patients received 4,000 IU of vitamin D per day and the other group received 400 IU of vitamin D per day. The high-dose group had a median delay of 13 months before their disease progressed, and the low-dose group had a median delay of 11 months. Patients in the high-dose group were also 36% less likely to have disease progression or death during the follow up period of 22.9 months.

“The results of our trial suggest an improved outcome for patients who received vitamin D supplementation, and we look forward to launching a larger trial to confirm these exciting and provocative findings,” said Charles Fuchs, MD, MPH, formerly of Dana-Farber as senior author of the study and now Director of the Yale Cancer Center.

Vitamin D is necessary for bone health and is made by the body through a chemical reaction that depends on sun exposure and is also found in some foods. Laboratory studies have shown vitamin D to have anti-cancer properties, including triggering programmed cell death, inhibiting cancer cell growth and reducing metastatic potential.

Further analysis of the results found that the of high-doses of vitamin D were less beneficial to patients who were overweight or whose tumors contained a mutated KRAS gene. These findings suggest “that certain subsets of patients may need even higher doses of vitamin D for anti-tumor activity,” according to researchers.

Kimmie Ng, corresponding author of the SUNSHINE study, feels that the findings are important because “it identifies a cost-effective, safe, and easily accessible agent as a potential new treatment for metastatic colorectal cancer. This could therefore potentially have a large and wide-reaching impact globally, regardless of a patient’s socioeconomic status or a country’s resources.”

Helicase May be Next Cancer Treatment Target

Understanding DNA mutations is the backbone of cancer research, and many recent studies have focused on new ways to combat these mutations. A study published in Nature, led by members of the Cancer Dependency Map (DepMap) Project, found that the WRN gene is a molecular vulnerability shared by several cancer types, including colon, gastric, endometrial and ovarian.

Cells with a WRN dependency have a genetic feature called a microsatellite instability (MSI). This predisposition to mutation is only seen in cancer cells and is caused by a breakdown of one of the cell’s methods for repairing damaged DNA, called mismatch repair. Approximately 15% of colon cancers, 22% of gastric cancers, 20-30% of endometrial cancers and 12% of ovarian cancers diagnosed each year lack mismatch repair and possess MSI features.

About half of cancers with MSI features can be treated using checkpoint inhibitors. The DepMap research team focused on cancers that are unresponsive to checkpoint inhibitors to determine if the loss of mismatch repair activity that leads to MSI causes genetic dependencies in tumor cells. To study this phenomenon, researchers examined two genome-scale datasets: a CRISPR-Cas9 gene dataset from the DepMap project and an RNA set created by Project DRIVE.

There were 900 cancer cell lines in these datasets, 51 of which the researchers classified as MSI. Of these, the team found that 73% of the MSI lines depended on WRN. They also found that non-MSI cancer cell lines were relatively unaffected by WRN loss. When the team changed cells to turn off WRN expression, they discovered MSI cancers grew slower, but healthy cells were unaffected.

WRN creates a helicase, an enzyme that helps cells interpret DNA. No drugs currently exist to attack WRN, but it may soon become a target given the study’s results. Since the study showed that healthy, genetically stable cells can withstand the loss of WRN, drugs created to block the enzyme should impact cancer cells that are dependent on the enzyme without harming healthy cells. The loss of WRN can lead to Werner Syndrome, but researchers believe using medications for a short period of time should mitigate this risk.

“We’re hopeful that these findings will spark excitement among other academic and drug discovery teams, and that we can help push forward a treatment that will make a difference in patients,” co-senior author and DepMap associate director Francisca Vazquez said. “And more broadly, these findings illustrate how a cancer dependency map can help identify therapeutic targets and accelerate the development of precision cancer medicine.”