New mRNA-based therapy acts against cancer stem cells

A gene therapy approach to preventing cancer metastases in prostate cancer or lung cancer appears to work better in research results and more resistant against a range of attempted mutations, as well as distinct cell populations and different cell types.

The pivotal results of this phase 2 randomized clinical trial were published today in The BMJ and provide strong evidence that the approach showed statistically significant benefit. If adopted it may provide a new scenario in cancer therapy, and inform the development and course of patients’ care.

Cancer cells in the final stages of cancer metastases can become tumor cells that are resistant to both prior and frequent pharmacological treatments, sometimes reaching the stage of complete cancer disease. That in turn may give rise to metastasis in the body.

The waiting period in most trials is often a matter of several years. Timing of drug treatment (tribipenematose or tamoxifen) is also an important factor when prescribing an earlier or more effective therapy. Vaccination, however, is not always a successful method of preventing metastatic tumors and the reasons for that are still unclear. Earlier trials have shown a significant benefit on tumor detection and progression.

To benefit patients, doctors also want to avoid patients’ cancers contributing to bias in results assessment. They also want to improve outcomes by identifying patients who need earlier treatment and who were resistant to other approaches. The latency period for patients with cancer stem cells and in preventing tumors from causing local resistance is about 5 years, and the need to confirm this is critical because, on average, about half of patients testing positive for a tumor are subsequently diagnosed with a subtype of cancer.

In this trial, which was headed by researchers at the Imperial College London and funded by the National Institute for Health Research (NIHR), between 2585 and 3290 patients were treated with 4. 5-fluorouracil, an agent that inhibits the ability of cancer stem cells to differentiate into other cells – the gametes. The trial involved 243 patients (27 of whom were randomized to receive the agent first) and 323 patients with prostate cancer and 512 in liver cancer. Seven patients with liver cancer were followed for 15 months, while in the remaining 73 patients only they were tested for 9 months.

The treatment was started at 200 mg/d, after which patients either maintained tumor growth for at least 15 months, or were switched to a placebo.

During that time, patients had:

The investigators found no significant difference in this outcome between patients on either treatment group – all differences were statistically significant. Even those who received the drug in the top tertile for latency compared with those in the lowest tertile had nearly half the improvement in relapse (or recurrence) rates for at least one primary tumor, compared with placebo (relative improvement trend, 0. 06).

And:

The level of improvement in latency was greater among patients in the top tertile for tumour growth compared with those in the bottom one-tenth of patients. The co-primary endpoint showed a significant main effect of treatment in the top tertile compared with participants in the bottom one-tenth of the group.

Because immunotherapies produce remission from cancer, and because tolerance may only develop a little bit more often with immunotherapies, extending treatment in patients with cancer that has not completely “cured” still more typically means significantly better outcomes.

Dr. Roger Nandy, compa-tive director of the FDA-approved drug drug property TNF, said: “TNF effectively stokes the fire of the way cancer evolves towards metastasis with scalpel-like attack. “