Medications, such as chemotherapy, are often limited by their tendency to be detrimental to healthy cells as an unintended side effect. Now research in the November 18th issue of Cell Press's Biophysical Journal offers a new computational model that can help investigators design ways to direct drugs to their specific targets.

A major problem with many cancer drugs is the harmful effects they can have on normal cells. Similarly, treatments for a variety of other diseases can have side effects by acting on cells that are not meant to be targeted. Researchers have tried to overcome this by linking drugs to antibodies, for example by linking a chemotherapy agent to an antibody that specifically attaches to cancer cells to create a fusion protein. However, it can be difficult to do so without compromising the medication's effectiveness because the drug has to be able to reach its targeted cell receptor at the same time as the antibody binds to its own target on the cell.

Investigators have now developed a computational model to help design the most effective way to link an antibody to a therapeutic drug to create such a fusion protein. The model takes into consideration how the length of an antibody linker will affect a drug's ability to interact with its target and uses this information as well as other parameters to model and predict how a particular fusion protein will look geometrically, how it will act when applied to cells, and what concentration is optimal.

"The importance of this finding is that it has the potential to allow us to predict the behavior of fusion proteins without having to physically make them, eliminating unsuccessful candidates for drug design using modeling and thereby saving time and effort," explains senior author Dr. Pamela Silver, of Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering at Harvard University. Therefore, accurately modeling the behavior associated with a given design for a fusion protein could allow researchers to move away from a screening-based, guess-and-check method to one that is based on rational design. "Using modeling as a first step of validation will allow us to determine which constructs are likely to be promising and focus our efforts on the best candidates for testing," says lead author Dr. Avi Robinson-Mosher, of the Wyss Institute.

African Americans, Hispanics, and those who receive care at a community hospital are all significantly less likely than other patients to receive treatment for early stage non-small cell lung cancer, according to a report in the Journal of Thoracic Oncology.

"We found significant disparities for treatment of a curable cancer based on race, insurance status, and whether or not treatment was at an academic or community hospital," said Dr. Matthew Koshy, a physician in the department of radiation oncology at the University of Illinois at Chicago College of Medicine, and lead author of the study. "Reducing these disparities could lead to significant improvements in survival for many people with inoperable early stage lung cancer."

The study is the largest to date looking at treatment received by patients with stage I non-small cell lung cancer, an early stage of lung cancer that has not spread to the lymph nodes and is characterized by a small nodules in the lung tissue. Treatment during this early stage offers the best chance for long-term survival.

Surgery to remove cancerous nodules in the lungs is the standard treatment for patients with stage I NSCLC. But many patients cannot undergo surgery, due to complicating medical conditions such as poor lung function or heart disease.

For those patients, radiation therapy has been the standard treatment, but outcomes are much poorer than for surgical treatment. Many patients deemed inoperable are only monitored, because the benefits of conventional radiation are regarded as minimal.

Over the last 10 years, a new radiation technology called stereotactic body radiotherapy, or SBRT, has replaced conventional radiation as the standard treatment for inoperable stage I NSCLC. It delivers much higher doses of radiation, requires fewer treatments, is better tolerated, and has survival outcomes comparable to surgery.

Koshy and his colleagues wanted to know if any factors predicted whether a patient was more likely to be observed, treated with conventional radiation, or treated with SBRT -- and if there were any disparities in the use of those treatments.

Researchers determine higher hospital and surgeon volume lead to better outcomes when treating bladder cancer patients

In a new, in-depth research project, Queen's professors Rob Siemens (Urology) and Christopher Booth (Cancer Care and Epidemiology) investigated what affect higher volume hospitals and surgeons had on the outcomes of patients undergoing a radical cystectomy for bladder cancer in Ontario.

Using data provided by the Institute for Clinical Evaluative Sciences (ICES) the investigators studied 2,802 patients who underwent the procedure between 1994 and 2008 in Ontario and found that higher volume hospital and surgeons were associated with less post-operative complications and better overall survival.

"These results are intriguing and will undoubtedly lead to some controversy in their interpretation," says Dr. Siemens. "We wondered if the processes and interactions that lead to better outcomes for patients treated by higher volume providers can be studied and identified, perhaps leading to improved outcomes for all if adopted by lower volume hospitals and surgeons."

The recent study explored a number of different aspects of bladder cancer care to better understand how quality surgical care is delivered for patients with advanced bladder cancer. The explanations for this volume-outcome relationship still remain mostly unidentified which could be a research project in the future.

"This research has only been able to illuminate a small fraction of the factors that explain the improved outcomes of higher volume providers," says Dr. Siemens. "Some would interpret this as a call to more aggressively support a policy of centralizing care at higher volume hospitals for complex medical/surgical diseases."

Siemens et al., (2014). Processes of Care and the Impact of Surgical Volumes on Cancer-specific Survival: A Population-based Study in Bladder Cancer. Urology, 84: 1049–1057 [Abstract]

Pain is a common symptom of cancer and side effect of cancer treatment, and treating cancer-related pain is often a challenge for health care providers. The Penny George Institute for Health and Healing researchers found that integrative medicine therapies can substantially decrease pain and anxiety for hospitalized cancer patients. Their findings are published in the Journal of the National Cancer Institute Monographs.

"Following Integrative medicine interventions, such as medical massage, acupuncture, guided imagery or relaxation response intervention, cancer patients experienced a reduction in pain by an average of 47 percent and anxiety by 56 percent," said Jill Johnson, Ph.D., M.P.H., lead author and Senior Scientific Advisor at the Penny George Institute.

"The size of these reductions is clinically important, because theoretically, these therapies can be as effective as medications, which is the next step of our research," said Jeffery Dusek, Ph.D., senior author and Research Director for the Penny George Institute.

Around 5,000 cases of ductal carcinoma in situ (DCIS), a condition where cancerous cells are contained within the milk ducts of the breast, are diagnosed each year in the UK, with two thirds diagnosed through breast screening. If left untreated, up to half of DCIS cases could progress into invasive breast cancer, but it is not possible to say which ones, so all women are offered treatment.

This usually involves breast-conserving surgery (lumpectomy) and, to reduce the risk of the cancer returning, radiotherapy to kill any remaining cancer cells. Even with treatment, however, up to one in five patients will see their DCIS come back, either as DCIS or as invasive breast cancer.

Now researchers from The University of Manchester and University Hospital of South Manchester NHS Foundation Trust - both part of the Manchester Cancer Research Centre - have investigated the role of a molecule known as  focal adhesion kinase (FAK) in controlling the resistance of DCIS to radiation and in predicting disease recurrence.

Dr Gillian Farnie, whose work at the University's Institute of Cancer Sciences was funded by a five-year £500,000 Breast Cancer Campaign Scientific Fellowship, said: "We know that cancer stem cells are able to avoid or repair damage caused by treatment. We wanted to look at how FAK is involved in this treatment resistance."

The team found that cancer cell samples containing more cancer stem cells had increased levels of FAK and that these samples were better able to survive radiotherapy. By examining patient tissue samples and information about whether each person had had a recurrence, the scientists discovered that high FAK activity was linked to the disease returning, either as DCIS or invasive breast cancer.

In further work, a drug that blocks FAK reduced the formation of mammospheres, or clumps of breast cancer stem cells, showing FAK is important in cancer stem cell activity. By combining this inhibition of FAK with radiotherapy, the group was able to achieve a greater treatment effect than with either therapy alone.