Paul Wong, Class of 2021
In the relentless race towards the cure for cancer, the multi-faceted approach of the scientific community has seemingly exhausted all avenues of treatments, ranging from shooting beams of concentrated electromagnetic energy in radiation to utilizing our own immune cells to fight cancer through immunotherapy. Furthermore, the treatment of cancer through these methods comes at a great burden to the patient, including fatigue, nausea, and vomiting. However, scientists from University of Melbourne have curated an unprecedented treatment that bypasses the harmful side effects of current cancer treatments—putting malignant cancer cells to sleep.
Dr. Anne Voss and Dr. Tim Thomas of the Walter and Eliza Hall Institute and University of Melbourne have spearheaded the recent efforts to develop “an entirely new weapon for fighting cancer” (1). The new class of cancer drugs target the histone acetyltransferases proteins, KAT6A/B, and in turn, induce cellular senescence, which is a state in which cells cease to divide (2). This phenomenon was originally discovered in the 1960’s by American scientists, Leonard Hayflick and Paul Moorhead, who were studying the process in which normal human fetal fibroblasts stop dividing in cell cultures. In their experiments, Hayflick and Moorhead investigated the ability for cell cultures to stop multiplying in numbers and found the theoretical limit, deemed the Hayflick Limit, which corresponds to approximately 50 cell population doublings. Prior to the work of Hayflick and Moorhead, their predecessors had accepted the fact that even normal cells, let alone cancerous cells, were immortal and could divide indefinitely (3).
The discovery of cell senescence was largely discovered in in vitro studies but its application to human bodies as been observed as well. It has been previously reported that senescence plays a role in other complex biological processes, such as development, ageing, and age related disorders (4). However, this concept can be extrapolated to malignant cancer cells in order to prevent the incessant division of tumors.
In the scope of cell division in cancer, the inhibition of lysine acetyltransferases (KATs) hinder the addition of an acetyl group onto histones, thus impeding the beginning of the division of cells. Lysine acetylation, which is facilitated by KAT proteins, is a reversible protein modification that has been linked with a variety of disease (5). When compared to chemotherapy and radiotherapy treatments for cancer, this new class of drugs poses an advantage in preventing potential side effects as cell senescence does not cause inadvertent, permanent DNA damage to cells but rather just puts the cancer cells to sleep.
The researchers at University of Melbourne originally shifted their focus towards the protein KAT6A after discovering the protein’s significance in an in vivo system using animal models (6). After genetically depleting the KAT6A protein in the animals, the life expectancy of the animals was seen to be quadrupled, thus leading to the conclusion that KAT6A is an important driver of cancer.
Currently, the class of cancer drugs is in the preclinical stage and has proven to show great promise in delaying or stopping relapse of various types of cancers without harmful side effects. Without the heavy cost of side effects that current treatments of cancer implicate, more patients may be inclined to undergo cancer treatment using KAT6 inhibitors. In addition, the ability of KAT6 inhibitors to inhibit relapse of cancer could be complemented by chemotherapy or radiotherapy to create combination treatments that would provide a more effective option of care for cancer. While still presenting as a novel treatment option with immense potential, there nevertheless remains a long road ahead for KAT6 inhibitors to prove to the scientific and medical communities as a viable alternative to current cancer-fighting drugs.
References
Dr. Anne Voss and Dr. Tim Thomas of the Walter and Eliza Hall Institute and University of Melbourne have spearheaded the recent efforts to develop “an entirely new weapon for fighting cancer” (1). The new class of cancer drugs target the histone acetyltransferases proteins, KAT6A/B, and in turn, induce cellular senescence, which is a state in which cells cease to divide (2). This phenomenon was originally discovered in the 1960’s by American scientists, Leonard Hayflick and Paul Moorhead, who were studying the process in which normal human fetal fibroblasts stop dividing in cell cultures. In their experiments, Hayflick and Moorhead investigated the ability for cell cultures to stop multiplying in numbers and found the theoretical limit, deemed the Hayflick Limit, which corresponds to approximately 50 cell population doublings. Prior to the work of Hayflick and Moorhead, their predecessors had accepted the fact that even normal cells, let alone cancerous cells, were immortal and could divide indefinitely (3).
The discovery of cell senescence was largely discovered in in vitro studies but its application to human bodies as been observed as well. It has been previously reported that senescence plays a role in other complex biological processes, such as development, ageing, and age related disorders (4). However, this concept can be extrapolated to malignant cancer cells in order to prevent the incessant division of tumors.
In the scope of cell division in cancer, the inhibition of lysine acetyltransferases (KATs) hinder the addition of an acetyl group onto histones, thus impeding the beginning of the division of cells. Lysine acetylation, which is facilitated by KAT proteins, is a reversible protein modification that has been linked with a variety of disease (5). When compared to chemotherapy and radiotherapy treatments for cancer, this new class of drugs poses an advantage in preventing potential side effects as cell senescence does not cause inadvertent, permanent DNA damage to cells but rather just puts the cancer cells to sleep.
The researchers at University of Melbourne originally shifted their focus towards the protein KAT6A after discovering the protein’s significance in an in vivo system using animal models (6). After genetically depleting the KAT6A protein in the animals, the life expectancy of the animals was seen to be quadrupled, thus leading to the conclusion that KAT6A is an important driver of cancer.
Currently, the class of cancer drugs is in the preclinical stage and has proven to show great promise in delaying or stopping relapse of various types of cancers without harmful side effects. Without the heavy cost of side effects that current treatments of cancer implicate, more patients may be inclined to undergo cancer treatment using KAT6 inhibitors. In addition, the ability of KAT6 inhibitors to inhibit relapse of cancer could be complemented by chemotherapy or radiotherapy to create combination treatments that would provide a more effective option of care for cancer. While still presenting as a novel treatment option with immense potential, there nevertheless remains a long road ahead for KAT6 inhibitors to prove to the scientific and medical communities as a viable alternative to current cancer-fighting drugs.
References
- Trounson A, University of Melbourne. 2019 Mar 11. Putting cancer cells to sleep. Pursuit. https://pursuit.unimelb.edu.au/articles/putting-cancer-cells-to-sleep
- Baell JB, Leaver DJ, Hermans SJ, Kelly GL, Brennan MS, Downer NL, Nguyen N, Wichmann J, McRae HM, Yang Y, et al. 2018 Aug 1. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature News. https://www.nature.com/articles/s41586-018-0387-5
- Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nature News. https://www.nature.com/articles/35036093
- Huang F, Abmayr SM, Workman JL. 2016 Jul 15. Regulation of KAT6 Acetyltransferases and Their Roles in Cell Cycle Progression, Stem Cell Maintenance, and Human Disease. Molecular and Cellular Biology. https://mcb.asm.org/content/36/14/1900
- Huang F. 2018 Nov 2. New KAT6 inhibitors induce senescence and arrest cancer growth. Synthetic and systems biotechnology. [accessed 2019 Mar 15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215967/
- staff SX. 2018 Oct 4. The drug that can put some cancer cells to sleep. Medical Xpress - medical research advances and health news. https://medicalxpress.com/news/2018-10-drug-cancer-cells.html
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