A team of researchers has identified key events that prompt certain cancer cells to develop resistance to otherwise lethal therapies.

By mapping the specific steps that cells of melanoma, breast cancer and a blood cancer called myelofibrosis use to become resistant to drugs, the researchers now have much better targets for blocking those pathways and keeping current therapies effective. The findings are published in two papers in the journal Science Signaling.

"Clinical resistance to anticancer therapies is a major problem," said lead author Kris Wood, Ph.D., assistant professor of Pharmacology and Cancer Biology at Duke. "The most logical way to solve the problem is to understand why tumor cells become resistant to drugs, and develop strategies to thwart these processes."

"In our studies, we developed a screening technology that allows us to quickly identify the routes cells can use to become resistant, and using that information, we were able to show that these mechanisms seen in the laboratory are actually also occurring in patients' tumors," Wood said.

New insights for patient decision-making, suggests study in plastic and reconstructive surgery

For women who have undergone mastectomy, breast reconstruction using the patient's own tissues, rather than implants, provides higher satisfaction scores, reports a study in Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS).

But the findings may at least partly reflect differences in the characteristics of women choosing different options for breast reconstruction, according to the study by plastic surgeon Dr. Yassir Eltahir and colleagues of University Medical Center Groningen, the Netherlands.

Higher Satisfaction Score with Autologous Breast Reconstruction

The researchers used the recently developed "BREAST-Q" questionnaire to analyze patient satisfaction and quality of life after breast reconstruction. The BREAST-Q was designed to gauge these important outcomes from the patient's point of view.

The study included BREAST-Q surveys completed by 92 women who had breast reconstruction between 2006 and 2010. Forty-seven women underwent autologous reconstruction, with the patient's own tissues--generally "donor" flaps from the abdomen--used to create the new breast. The remaining 45 women underwent alloplastic reconstruction, using implants.

The results suggested that women choosing reconstruction with their own tissues were more satisfied with the results. Scores for satisfaction with the reconstructed breasts averaged about 75 (on a 100-point scale) after autologous reconstruction versus 65.5 for implant-based reconstruction.

Overall patient satisfaction scores were also higher with autologous reconstruction: about 82 versus 74.5. Scores for various aspects of quality of life--including psychosocial, sexual, and physical well-being--were not significantly different between groups.

The risk of developing leukemia after radiation therapy or chemotherapy for early stage breast cancer remains very small, but it is twice as high as previously reported, according to results of a new study led by researchers at the Johns Hopkins Kimmel Cancer Center.

The study team reviewed data on 20,063 breast cancer patients treated at eight U.S. cancer centers between 1998 and 2007 whose cancer recurrence and secondary cancer rates were recorded in a database kept by the National Comprehensive Cancer Network. In that group, 50 patients had developed some form of leukemia within 10 years after radiation therapy, chemotherapy or a combination of the two. That translates to roughly a cumulative risk of 0.5 percent.

Data from earlier randomized clinical trials, which typically include just a few hundred patients, found that about 0.25 percent of breast cancer patients develop leukemia as a late effect of chemotherapy, says Judith Karp, M.D., professor emerita of oncology at the Johns Hopkins University School of Medicine, who retired in 2013 as director of the Kimmel Cancer Center's Leukemia Program. Results  were published online in the Journal of Clinical Oncology.

"The frequency of bone marrow cancers such as leukemia is small, there's no question about it," Karp says. "However, the cumulative risk over a decade is now shown to be twice as high as we thought it was, and that risk doesn't seem to slow down five years after treatment."

"Most medical oncologists have come to think that the risk is early and short-lived," says Karp. "So this was a little bit of a wake-up call that we are not seeing any plateau of that risk, and it is higher."

Antonio Wolff, M.D., a professor of oncology at the Johns Hopkins University School of Medicine, says the study could help early-stage breast cancer patients and their physicians think more carefully about the use of chemotherapy for "just-in-case" reasons, especially when patients have a low risk of cancer recurrence.

"Our study provides useful information for physicians and patients to consider a potential downside of preventive or adjuvant chemotherapy in patients with very low risk of breast cancer recurrence," says Wolff. "It could be a false and dangerous security blanket to some patients by exposing them to a small risk of serious late effects with little or no real benefit from the treatment."

St. Jude Children's Research Hospital study identifies small group of patients at risk for intellectual decline after bone marrow transplantation; results set stage for new strategies to preserve IQ and fight cancer.

Toddlers who undergo total body irradiation in preparation for bone marrow transplantation are at higher risk for a decline in IQ and may be candidates for stepped up interventions to preserve intellectual functioning, St. Jude Children's Research Hospital investigators reported. The findings appear in the current issue of the Journal of Clinical Oncology.

The results clarify the risk of intellectual decline faced by children, teenagers and young adults following bone marrow transplantation. The procedure is used for treatment of cancer and other diseases. It involves replacing the patient's own blood-producing stem cells with those from a healthy donor.

Researchers tracked IQ scores of 170 St. Jude patients before and for five years after transplantation, making this the most comprehensive effort yet to determine how the procedure affects intelligence. The patients ranged in age from 4 months to 23 years when their transplants occurred. The procedure had little lasting impact on the IQ scores of most patients.

"For the great majority of patients, these findings provide reassurance that transplantation will not have a significant negative impact on cognitive development," said corresponding author Sean Phipps, Ph.D., chair of the St. Jude Department of Psychology. "We have also identified a high-risk group of younger patients who may benefit from more intensive interventions, including developmental stimulation and other rehabilitative therapies designed to prevent a decline in intellectual functioning and aid in recovery."

A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. 

The findings of the randomized study were presented at the 2014 San Antonio Breast Cancer Symposium, by Kerin Adelson, M.D., assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven.

The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Doris Germain of Mt. Sinai Hospital, found that the combination of the drugs bortezomib and fulvestrant, versus fulvestrant alone, doubled the rate of survival at 12 months and reduced the chance of cancer progression overall.

The receptor CCR5, targeted by HIV drugs, is also key in driving prostate cancer metastases, suggesting that blocking this molecule could slow prostate cancer spread.

Although prostate cancer can be successfully treated in many men, when the disease metastasizes to the bone, it is eventually lethal. In a study published online December 1st in the journalCancer Research, researchers show that the receptor CCR5 best known for its role in HIV therapy, may also be involved in driving the spread of prostate cancer to the bone.

"Because this work shows we can dramatically reduce metastasis in pre-clinical models, and because the drug is already FDA approved for HIV treatment- we may be able to test soon whether this drug can block metastasis in patients with prostate cancer," says Richard Pestell, M.D., Ph.D., MBA, Director of the Sidney Kimmel Cancer Center at Thomas Jefferson University and senior author on the study.

The work builds on previous research from Dr. Pestell's lab that showed in 2012 that CCR5 signaling was key in the spread of aggressive forms of breast cancer to the lungs. Their prior paper demonstrated that breast cancer cells that carried the CCR5 receptor on their surface were drawn to the lung. Given that prostate cancer cells were attracted to the bone and brain, Pestell's team investigated whether CCR5 could play a role in prostate cancer metastases as well.

The research was complicated by the fact that there was no immune competent mouse model of prostate cancer that reliably developed bone and brain metastases. So the researchers developed a prostate cancer cell line, driven by an upregulated Src gene, that regularly caused bone metastases in immune-competent mouse models. Because the immune system is so important in human prostate cancer it was important to develop a model that reflected human disease.

The five-year survival rate for advanced-stage laryngeal cancer was higher than national levels in a small study at a single academic center performing a high rate of surgical therapy, including a total laryngectomy (removal of the voice box), to treat the disease, despite a national trend toward organ preservation, according to a report published online by JAMA Otolaryngology-Head & Neck Surgery.

The larynx is a common site of head and neck cancer with more than 10,000 cases annually. Over the past two decades, treatment for advanced-stage laryngeal cancer has shifted from primary surgical therapy to organ preservation treatments with chemotherapy and radiation, according to study background.

Blake Joseph LeBlanc, M.D., of Louisiana State University Health-Shreveport (LSU Health), and co-authors examined survival rates at their institution for primary surgical treatment of advanced-stage tumor with outcomes in the National Cancer Database (NCDB).