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Exciting breakthroughs in cancer cures

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*Herceptin treats disease 200% better as lowering cholesterol improves tumour-fighting immunotherapy
*Viagra, flu vaccine combo now being tested in humans after reducing ailment by 90% in mice, says study

Women with aggressive breast cancer can be effectively cured in half the time compared to current treatment, minimising harmful side effects, researchers have said.A new trial of patients suffering from HER2-positive breast cancer found survival rates were almost identical among those given six months of therapy compared with a year.

Around one in five cases of breast cancer is characterised by an excess of the HER2 protein, which has traditionally made affected women harder to treat.But Trastuzumab, commonly known by its brand name Herceptin, has significantly improved survival for HER2-positive patients since 2005.However, the medication can prompt a range of side effects ranging from high temperatures to heart problems, which often become more severe the longer treatment goes on.

In the new study, to be presented at the American Society of Clinical Oncology in Chicago, researchers at Cambridge University examined the outcomes of 4,088 women with early-stage HER2-positive breast cancer who were being treated with Herceptin.The disease-free survival rate at four years was 89.4 per cent in those given six months’ treatment, compared to 89.8 per cent in those who underwent the standard 12 months.

Additionally, only four per cent of the women in the six-month cohort were forced to stop using herceptin due to cardiac problems, half the proportion of those in the 12-month cohort.

Also combination of Viagra and a flu vaccine could treat cancer, surprising new research suggests. The unconventional strategy invigorates the immune system to attack tumor cells left lingering after surgery, when the body is vulnerable.Testing the method in mice with lung cancer, Canadian researchers saw a 90 percent reduction in the spread of the disease.

The study was such a success that 24 human stomach cancer patients will now test the combination in a clinical trial that could pave the way to it being approved.
Normally, immune cells called natural killer cells play a major role in killing metastatic cancer cells. But surgery causes another kind of immune cell, called a myeloid derived suppressor cell (MDSC), to block the NK cells.

A new study has found that when cholesterol levels are reduced, cancer immunotherapy becomes more effective. The findings offer a simple way to improve this fledgling technology.Lowering cholesterol may improve cancer outcomes in the future. Immunotherapy is a fairly new but successful method of treating cancer. It uses the body’s own immune system to fight cancerous cells.

Scientists are currently investigating a range of immunotherapies that use a variety of tactics.Some types work to enhance the body’s natural immune response against cancer cells, and this is known as passive immunization.

Other versions actively direct the immune system to attack specific proteins on cancer cells, and these are called active immunotherapies.One type of passive immunization — adoptive T cell transfer — involves engineering T cells to home in on a specific cancer type before transplanting them into the patient.

Adoptive T cell transfer is still a relatively new technology. In fact, the first two procedures of this type to be used in the United States were only approved by the Food and Drug Administration (FDA) in 2017.

As such, scientists are still working out how to enhance the therapy and make it as effective as possible. For instance, researchers are currently investigating the use of different methods to transplant the T cells, as well as how combining the therapy with other drugs might improve outcomes.Professor Helena Earl, who led the Cambridge researchers, said: “We are confident that this will mark the first steps towards a reduction in treatment duration for many women with HER2-positive breast cancer.

“Everyone involved in this study is very excited by these results.”The new analysis, taken from data gathered as part of the Persephone trial, is the largest to date to examine the impact of shortening the duration of Herceptin treatment, according to the authors.Other scientists cautioned, however, that the study’s follow-up period has been relatively short and that further research will need to analyse longer-term survival rates.

The study was funded by the National Institute for Health Research, a body overseen by the United Kingdom (UK) Government.Dr. Rebecca Auer’s team at the University of Ottawa has found that erectile dysfunction drugs block these suppressor cells, which allows the natural killer cells to do their cancer-fighting job.

The flu vaccine works to further stimulates the natural killer cells.“Surgery is very effective in removing solid tumours,” said senior author Dr. Auer, surgical oncologist and head of cancer research at The Ottawa Hospital.“However, we’re now realizing that, tragically, surgery can also suppress the immune system in a way that makes it easier for any remaining cancer cells to persist and spread to other organs.

“Our research suggests that combining erectile dysfunction drugs with the flu vaccine may be able to block this phenomenon and help prevent cancer from coming back after surgery.”The current study investigated sildenafil (Viagra), tadalafil (Cialis) and an inactivated influenza vaccine (Agriflu) in a mouse model that mimics the spread of cancer (metastasis) after surgery.

Dr. Auer is now leading the first clinical trial in the world of an erectile dysfunction drug (tadalafil) and the flu vaccine in people with cancer.It will involve 24 patients at The Ottawa Hospital undergoing abdominal cancer surgery.This trial is designed to evaluate safety and look for changes in the immune system.If successful, larger trials could look at possible benefits to patients.

Do the biological differences between men and women impact immunotherapy’s effectiveness?Dr. Qing Yi, Ph.D., from the Cleveland Clinic Lerner Research Institute in Ohio, is approaching this question from a slightly different angle. He is interested in how cholesterol may play a part in the success of adoptive T cell transfer.
The latest study from his laboratory is now published in the Journal of Experimental Medicine.

In previous work, Dr. Yi identified that a specific subtype of T cell — Tc9 cells — were more fiercely anti-cancer than others. Tc9 cells are known to excrete interleukin 9 (IL 9), a signaling molecule with anti-tumor properties.Building on this finding, Dr. Yi wanted to understand whether Tc9 cells could be enhanced further.

Using gene profiling — a technique that allows scientists to see which genes are “switched on” in a cell — they compared Tc9 cells with other subtypes of T cell. They found that Tc9 cells contained significantly less cholesterol. This, they thought, might be key to their improved cancer-fighting ability. So, they took their hunch to the laboratory and put it to the test.

To investigate, they added cholesterol-lowering drugs to cancer cells before treating them. As they expected, this had the effect of turning on anti-cancer pathways.In a second part of the study, they used a tumor-bearing animal model. They discovered that, when cholesterol levels were reduced before the course of immunotherapy began, there was a greater expression of IL 9, and its anti-tumor effects were more pronounced.

As the study authors explain, “Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function.”Dr. Yi is excited about the findings. He says, “Our studies suggest a relatively simple, cost-effective way to enhance T cell transfer therapy.” The scientists plan to continue their line of investigation and embark on clinical trials as soon as possible.


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