The Functions of Voltage-Gated Calcium Channels in Oesophageal Adenocarcinoma
Oesophageal cancer is the sixth deadliest cancer worldwide; in Ireland, less than 1 in 4 patients will survive five years after diagnosis. In this study, we will investigate certain genes and proteins which appear to be crucial for oesophageal cancer survival.
To make proteins, cells convert their genes to mRNA. This process is known as gene transcription. Cancer can change gene transcription within cells to benefit its own survival. Genes can be grouped into categories, including “calcium toolkit genes” involved in cell communication using calcium. These have a wide variety of roles in the body, including in cancer- changes to cellular calcium can cause cancer cells to grow faster, survive longer, and spread to other parts of the body. However, it may be possible to reverse these changes and achieve better outcomes for cancer patients.
Dr John Mackrill’s lab found that oesophageal cancer patients whose tumours overproduce certain calcium toolkit genes have a better probability of survival over time than those who transcribe them less. Two of these genes have been found in cell models of oesophageal cancer: voltage-gated calcium channel subunit α1D (CACNA1D) and α2D (CACNA2D4). We don’t know why or how these genes might work to improve survival in oesophageal cancer patients. Under Dr Mackrill’s supervision, I hope to understand how these genes might be related to oesophageal cancer development, and whether they can be targeted for treatment. We hope that this will allow oesophageal cancer patients, clinicians, and other scientists to better understand and treat the disease.
Cutliffe, Alana L., Sharon L. McKenna, Darshan S. Chandrashekar, Alvin Ng, Ginny Devonshire, Rebecca C. Fitzgerald, Tracey R. O’Donovan, and John J. Mackrill. “Alterations in the Ca2+ Toolkit in Oesophageal Adenocarcinoma.” Exploration of Targeted Anti-Tumor Therapy 2, no. 6 (2021): 543–75. https://doi.org/10.37349/etat.2021.00063.Back