Three new ways to target and treat various forms of cancer

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Originally posted on MIMS.

Treating cancer these days effectively doesn’t necessarily entail a cocktail of chemotherapy or radiotherapy for the patient. Often, the real challenge is to get certain regulatory cells out of the way, provide treatments when the time is right, or have a therapy that can give high doses of radiation safely. Here are three such new methods that are seeking to change treatments for the better.

1. Near-infrared photoimmunotherapy

In a method called near-infrared photoimmunotherapy, researchers in Japan and US have used an antibody-dye pair, activated by near-infrared light, to destroy immune-suppressing cells within a tumour. The antibody-dye pair targets one common type of regulatory T-cells called CD25+ Tregs, which modulate the immune system and maintain tolerance to self-antigens.

Shining near-infrared light on the tumour activates the antibody to target the Tregs for destruction. With the Tregs out of the way, the body’s usual immune cell defenders can enter and attack the tumour.

The researchers showed that the technique can shrink lung, colon, and prostate tumours in mice, and help destroy untreated tumours of the same type throughout the body. The effect lasts for about a week, but its widespread effects may make it useful for treating metastatic cancer, and repeated treatments may give the immune system time to learn how to protect against relapse of the cancer. Their study was published in Science Translational Medicine.

2. Hypoxia-activated prodrugs at the right time

The early bird might catch the worm, but the second mouse gets the cheese. With the right timing, medications known as hypoxia-activated prodrugs (HAPs) could help prevent drug resistance in a subtype of lung cancer, according to a study published in PLOS Computational Biology.

Typically, drugs are transported by blood vasculature to act on target tissue. However, with tumours that have poor vasculature, it is difficult for drugs to penetrate the tissue and do its work. HAPs are able to work around this problem because it kills cancer cells in hypoxic (low-oxygen) parts of a tumour. Still, HAPs have not yet shown significant benefits for patients in clinical trials. Danika Lindsay and Jasmine Foo of the University of Minnesota and their colleagues at the University of Southern California set out to investigate how to make HAPs more effective.

The researchers were interested in the development of drug resistance in non-small cell lung cancer (NSCLC) with a EGFR mutation since most people with this subtype develop resistance 12 to 18 months after receiving erlotinib as the standard treatment.

To monitor the development of drug resistance of the NSCLC subtype with a EGFR mutation, the researchers have built a mathematical model. It was used to explore different combinations of erlotinib and a HAP known as evofosfamide. A spectrum of dosages and schedules were tested to see which were the most effective in preventing erlotinib resistance in the virtual tumour cells.

Their findings show that among the combinations, the most effective were those that alternated between erlotinib and evofosfamide while minimising the time between each evofosfamide dose and the next erlotinib dose. In other words, the use of both drugs had better success at preventing drug resistance than either drug on its own.

“Use of hypoxia-activated prodrugs, if carefully timed in combination with current standard therapies, may be useful for eradicating tumours in NSCLC patients,” says study senior author Jasmine Foo.

Of course, these findings are only virtual simulations that can provide treatment guidelines to tackle the problem of drug resistance. The authors say that this strategy must be validated by preclinical experiments before it can be tested in patients.

3. Proton beam therapy

After a decade of studying the technology for proton beam therapy to treat cancers, Singapore is investing close to $100 million on a proton beam therapy machine which causes much less damage to healthy tissue than current radiation therapy. Up until now, the cost and size of the machine have been major inhibitors for the National Cancer Centre Singapore (NCCS) to set up a proton beam therapy machine, the first to be launched in Southeast Asia.

According to Dr Fong Kam Wend, head of radiation oncology at NCCS, proton beam therapy is particularly good for treating brain cancer, especially in children. The machine will also be used on young adults for cancers in the head, and on patients who have suffered a relapse despite having radiation therapy previously.

Current treatments of radiation therapy using X-rays cannot avoid some damage to the brain. In radiation therapy, the intense amounts of energy directed at cancer cells also destroy surrounding healthy cells. Although doctors often reduce X-ray doses to protect surrounding healthy tissue from harm, patients that survive might suffer from a range of side effects, including mental retardation, stunting and hormonal imbalance.

However, according to Professor Soo Khee Chee, director of NCCS, the use of proton beam therapy presents patients with “significantly reduced” side effects.

In proton therapy, energy is carried by positively charged particles in an atom called protons. The protons are raised to a high energy level (70% of the speed of light) through a particle accelerator. But unlike the photons in X-rays, proton beams stop after releasing their energy within their target. This makes the therapy finely controlled, so higher doses of radiation can be more safely delivered to tumours with less risk to healthy tissue. As such, compared to using X-rays, the chances of brain damage and retardation drops to less than half, and the chances of secondary cancers drop to about one-eight.

According to Soo, one machine can cater to a population of 25 million people. NCCS expects to treat 150 patients in the first year before building up to about 1,000 patients a year. Patients need 20 to 30 sessions, with the actual radiation treatment lasting less than two minutes each time. NCCS is also keen to know if higher doses can be given with the proton beam, since they can be more effective in killing cancer cells.

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