Molecular Mechanisms And Control Of Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$453,055.00
Summary
Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell fr ....Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell from dividing any further, and acts as a very potent barrier to the cell becoming cancerous. Some normal cells are not subject to this inexorable telomere shortening: these are the germ cells in the testis and ovary, that are responsible for passing on genetic material to the next generation. Such cells express an enzyme, telomerase, which is able to synthesise new telomeric DNA to replace that lost during cell division. 85% of human cancers are also able to prevent shortening of their telomeres - and thus have breached the barrier that normally prevents unlimited cell proliferation - via telomerase activity. Therefore, if drugs that inhibit telomerase can be developed they may be a very useful new form of cancer treatment. We have found, however, that some cancers are able to prevent telomere shortening by a process that does not involve telomerase, and which we refer to as Alternative Lengthening of Telomeres (ALT). One practical implication of this finding for the design of new cancer treatments is that telomerase inhibitors will need to be used in combination with ALT inhibitors. In this study, we will determine A. how normal cells keep the ALT mechanism permanently shut down and B. the molecular details of the ALT mechanism itself. An understanding of these processes may ultimately contribute to the development of novel cancer treatments that disrupt the ability of cancer cells to divide an unlimited number of times.Read moreRead less
The Role Of IQGAP1 In Human High-Grade Glioma And Its Regulation By MiR-124-A
Funder
National Health and Medical Research Council
Funding Amount
$69,137.00
Summary
Survival rates for many cancers are improving, however, for most patients diagnosed with a high grade glioma (HGG) there is limited long term survival. The treatments administered have limited effectiveness due to extensive infiltration of the tumour cells. New therapeutic strategies targeting the invading cell population to further reduce tumour spread are needed. Hence, a better understanding of the mechanisms promoting glioma migration and invasion are urgently required in this fatal disease.
TRF2 Protein And T-loop Replication In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Telomere loss acts as a clock telling cells when to stop proliferating. Cancer cells ignore this clock and grow indefinitely by preventing the normal loss of telomeres. Little is known about one of the methods cancers use to preserve telomeres, called ALT, which is employed by some brain tumours and other cancers. We will determine if the TRF2 protein is involved in controlling ALT. This will lay the basis for future anti-cancer treatments targeted at ALT.
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
Definition Of The Role Of Senescence In Tumour-associated Endothelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$583,081.00
Summary
'Cellular senescence' is a mechanism to stop cells growing, and it may protect against tumour growth. However, it may also induce changes in cells leading to 'pro-tumour' effects. We have identified a gene - which we have called SEN1 - which induces senescence in the blood vessels of tumours. This gene may cause alterations in the blood supply to the tumour allowing it to grow and to resist chemotherapy. Understanding this gene may allow us to treat cancer by shutting off its blood supply.
Dissecting The Function Of The Hedgehog-Patched Pathway In Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$606,811.00
Summary
There have been significant improvements in survival from breast cancer, particularly due to specialised treatments that target faulty pathways in the growth of cancer cells. One newly described, aggressive type of breast cancer called basal-like breast cancer lacks specialised treatment. We will determine whether the 'Hedgehog' signalling pathway is a suitable target for basal breast cancer therapy.
Regulation of tissue morphogenesis in reproductive function and metastatic cancer. Infertility, endocrine and metabolic disorders and reproductive cancers are all increasing medical problems and principal contributors to morbidity and mortality in the Australian community. This research takes the novel approach of investigating the mechanisms of dynamic remodeling in reproductive organs. Novel hormonally controlled mechanisms of tissue remodeling unique to reproductive organs and cancers in ad ....Regulation of tissue morphogenesis in reproductive function and metastatic cancer. Infertility, endocrine and metabolic disorders and reproductive cancers are all increasing medical problems and principal contributors to morbidity and mortality in the Australian community. This research takes the novel approach of investigating the mechanisms of dynamic remodeling in reproductive organs. Novel hormonally controlled mechanisms of tissue remodeling unique to reproductive organs and cancers in adults have been discovered. The results are being applied to new medical alternatives for infertile patients and new diagnostics and therapeutics for patients with metastatic cancers. The information is also being applied to improve reproductive efficiency in animal production industries.Read moreRead less
The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its developmen ....The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its development are unknown. This project aims to better understand the critical first step in the progression to cancer and thus expand the scope for the development of therapies, particularly those aimed at early intervention, and tools that predict progression.Read moreRead less