Science Bites seeks to compile the latest scientific research updates in bite-sized forms.

1. PD-L1 protein released by cancer cells to mask pain

A new study hypothesises that cancers may be masking tumour-induced pain allowing it to proliferate unnoticed. Ru-Rong Ji, a Duke University anaesthesiologist, led the study to observe the PD-L1 protein produced by cancer cells. It enables cancer cells to hide from immune cells and avoid destruction. During this research, Ji discovered their role in shutting off the pain system. These findings could aid in assessing the efficacy of immunotherapy treatments.

Ji worked on the theory that if a tumour becomes increasingly painful after immunotherapy, it indicates that the drug is effective. Essentially, it means the tumour cells are no longer using the PD-L1 protein as a pain-masking mechanism.

Researchers injected mice with nivolumab, preventing PD-L1 from binding to PD-1. Upon poking their paws, they found that mice with melanoma were more pain-sensitive. Conversely, scientists injected PD-L1 into the paws or spinal cord of mice where, interestingly, PD-L1 numbed the pain.

“The idea of using pain as an indicator to decide if a patient should receive a certain type of cancer treatment or take an alternative presents a lot of issues,” said vice president of clinical development at the Parker Institute for Cancer Immunotherapy, Dr Ramy Ibrahim. He added that pain is very subjective and pain receptors in mice differed greatly from humans. Other researchers noted that more pain did not indicate tumour shrinkage.

“We would need much more data in humans to clearly define and validate the applicability in cancer patients before this could even be considered as a decision-making tool,” explained Ibrahim.

2. Researchers are working on better treatment for AML

Scientists from the Australian National University (ANU) have successfully treated acute myeloid leukaemia (AML) in mice with a new treatment that proves to be better than standard chemotherapy regimens.

Dr Nadine Hein who is the lead researcher at ANU said, “Not only have we been able to reduce the number of cancer cells, we have been able to reduce the number of cancer stem cells that tend to develop or be resistant to chemotherapy and are thought to be responsible for disease relapse in patients.”

“We are working towards a treatment that will improve on the current chemotherapy options and improve the patient's prognosis,” continued Dr Hein.

The research team used a compound called CX-5461 to induce apoptosis besides specifically targeting protein synthesis in the cancer cells. A Canberra haematologist and Senior Lecturer at ANU, Dr James D'Rozario stated that the standard method of treating AML has been the same for the past three decades.

He explained, “Novel agents such as CX-5461 with more sophisticated mechanisms of action are desperately required to improve outcomes in patients with this group of illnesses.”

A Phase 1 clinical trial for patients with leukaemia has been completed in Australia after these promising pre-clinical trial findings. These results will be published later in the year. Professor Ross Hannan from ANU’s Department of Cancer Biology and Therapeutics added, “Another Phase 1/ Phase 2 clinical trial is underway in Canada for the treatment of patients with solid tumours.”

ZBTB48 binds through the last of its 11 zinc fingers directly to telomeric DNA. (PC: EurekAlert/ National University of Singapore)
ZBTB48 binds through the last of its 11 zinc fingers directly to telomeric DNA. (PC: EurekAlert/ National University of Singapore)

3. NUS scientists have isolated a gene to study its role in cancers

The journal EMBO Reports published a study last month conducted by the National University of Singapore(NUS) in collaboration with researchers at the TU Dresden and the Institute of Molecular Biology Mainz in Germany. The team revealed the function of the ZBTB48 gene in regulating telomeres and mitochondria. These findings will lead to a better understanding of human ageing and cancer progress.

Telomeres form protective caps at chromosome ends and shorten when a cell divides. The loss of telomeres leads to cellular senescence and cell death. Cancer cells have the ability of bypassing this mechanism and enabling continued cell proliferation.

This study uncovered this protein’s potential to not only inhibit growth in cells with abnormally long telomeres, which was already known, but also generally target cancer cells regardless of their telomere length.

Dr Grishma Rane, co-first author and Research Fellow at CSI Singapore said, “The findings from our study validated recent findings on the telomere binding role of ZBTB48. Our team's independent discovery of the ZBTB48 protein is an extension to these recent findings, as we found evidence indicating that cancer cells, in general, are regulated by ZBTB48. It potentially also suggests applications for the human ageing process even at old age when telomere length has already decreased.”

The team looks to further investigate the exact way this gene controls telomere length and its role in certain cancers, such as neuroblastoma, where the gene is commonly deleted. MIMS

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