This article highlights some of the most recent drug target discoveries that could be used to develop and design a treatment for pancreatic cancer.
Scientists investigating pancreatic cancer have identified new targets which, with further research, could be the basis for developing future therapies. Listed below are five of the most recent target discoveries, in order of their journal publication dates, with the newest first.
Scientists at the Queen Mary University of London, UK and Zhengzhou University, China have developed a personalised vaccine system that may be able to delay the onset of pancreatic cancer.
Cells taken from mice, mutated chemically into pancreatic cancer cells and then infected with Adenovirus (AdV) as a prime or Vaccinia virus (VV) as a boost, create a vaccine product. The virus kills the cancerous cells in such a way that their antigens are released and are therefore able to prime the immune system to prevent pancreatic cancer returning.
Injection of the virus-infected cells into mice destined to develop pancreatic cancer doubled their survival rate, compared to their unvaccinated counterparts. The vaccine also delayed the onset of the condition in these mice.
Using cells from the recipient of the vaccine enables the immune system to respond to the exact antigens seen in tumour cells of the individual, resulting in a vaccine regime tailored to them.
Through this international collaboration, we have made progress towards the development of a prophylactic cancer vaccine against pancreatic cancer, said Professor Yaohe Wang, leader of the study, from Queen Mary University of London and the Sino-British Research Centre at Zhengzhou University in China.
Researchers at Sanford Burnham Prebys Medical Discovery Institute in the US have identified that a combination of two anti-cancer compounds, already approved for use to treat other cancers, shrank pancreatic tumours in mice.
Our study identifies a potential treatment combination that can immediately be tested against these aggressive tumours. We are already meeting with oncologists at Oregon Health & Science University, US to discuss how to advance this discovery into clinical evaluation, explained Dr Zeev Ronai, a professor in Sanford Burnham Prebys Tumor Initiation and Maintenance Program, also senior author of the study.
Scientists used L-asparaginase to starve pancreatic tumours of asparagine, an amino acid required by cells for protein synthesis. However, the tumour cells did not die, instead switching on a stress response pathway whereby they could produce asparagine themselves. Scientists then used an MEK inhibitor to block the stress response pathway, causing the pancreatic tumour to shrink.
L-asparaginase is already US Food and Drug Administration (FDA) approved to treat leukaemias and similarly the MEK inhibitor is approved for the treatment of solid tumours, including melanoma skin cancer.
This research lays the basis for the inhibition of pancreatic tumour growth by a combined synergistic attack based on asparagine restriction and MAPK signalling inhibition, says Dr Eytan Ruppin, chief of the Cancer Data Science Library at the National Cancer Institute (NCI) and co-author of the study.
Scientists from the Max Planck Institute for Biology of Ageing, Germany have identified that YME1L, a protease in the membrane of mitochondria, is activated when a cell uses glycolysis to produce energy anaerobically.
scientists were able to reduce tumour growth by switching off the glycolysis signalling pathway in the mitochondria
Cells adapt to oxygen deficiency by switching their energy supply to glycolysis, which ferments sugar without oxygen. This switch is often necessary in old age, as the cells in the body become poorly supplied with oxygen and nutrients.
Cancer cells can also face this problem; prior to angiogenesis, tumours are poorly perfused and so the tissue is deprived of oxygen. Oxidative stress in tumours drives the switch-on of multiple pathways. This includes the glycolysis pathway that alters the behaviour of the mitochondria to provide tumour cells with energy despite being starved of oxygen.
Scientists found that the YME1L protease is activated during the conversion to glycolysis. YME1L appears altered and breaks down various proteins in the organelles, preventing the formation of new mitochondria and causing the remaining organelles to change their metabolism. This process eventually stops as YME1L begins to degrade itself at high activity.
Researchers examined cancer cells originating from patients with pancreatic tumours and were able to reduce tumour growth by switching off the glycolysis signalling pathway in the mitochondria, with reproducible results both in the petri dish and in pancreatic tumours in mice.
There is currently no treatment available for pancreatic cancer. I believe that this protease can be a very interesting therapeutic target because we have seen that the signalling pathway is also active in human patients with pancreatic cancer, explained Thomas Langer, the Max Planck Director, continuing: However, there are no known substances that have an effect on this protease.
Researchers at the Crick Institute have identified cancer stem cells as a driver of pancreatic cancer growth. These cells can metastasise and differentiate into different tumour types to continue the spread of cancer.
Cancer stem cells appear at all stages of cancer growth so being able to identify where they are present could be vital in both targeting cancer and developing new treatments, according to the researchers. Analysis of gene expression in the cancer stem cells identified a protein, CD9, is present on tumour surfaces during development and when it is more established. This protein could therefore be used as a marker to help locate these cells.
A further development of the study established that this protein is not just a marker of cancer stem cells, but also promotes their malignant behaviour. By altering the amount of CD9 in tumour cells in mice, researchers found that reduced levels of this protein caused smaller tumours to form and increasing levels of CD9 created more aggressive cells able to form large tumours quickly.
These cells are vital to pancreatic cancer and if even just a few of them survive chemotherapy, the cancer is able to bounce back. We need to find effective ways to remove these cells and so stop them from fuelling cancer growth. However, we need more experiments to validate the importance of CD9 in human pancreatic cancer, says Victoria Wang, lead author and member of the Adult Stem Cell Laboratory at the Crick Institute.
A look into cancer stem cell metabolism also revealed CD9 increases the rate tumour cells take up glutamine, an amino acid which helps provide energy for cancer growth.
Now we know this protein is both linked to cancer stem cells and helps cancer growth, this could guide the development of new treatments that are targeted at the protein and so cut off the supply of glutamine to cancer stem cells, effectively starving the cancer, says Axel Behrens, corresponding author and group leader in the Adult Stem Cell Laboratory at the Crick Institute.
Scientists at Tel Aviv University, Israel have found that PJ34, a small molecule, causes human pancreatic cancer cells to self-destruct. The researchers tested PJ34 on xenografts (transplants) of human pancreatic tumours in mice.
this mechanism also exists in other types of cancer and therefore the treatment could be valuable for use on those resistant to current therapies
The mice were treated with a molecule called PJ34, which is permeable in the cell membrane but affects human cancer cells exclusively. This molecule causes an anomaly during the duplication of human cancer cells, provoking their rapid cell death. Thus, cell multiplication itself resulted in cell death in the treated cancer cells, explains Professor Malca Cohen-Armon, project lead at Tel Aviv Universitys Sackler Faculty of Medicine.
The treatment consisted of daily PJ34 injections for 14 days and four weeks later there was a relative drop of 90 percent in the number of cancer cells within the tumours of the mice. Cohen-Armon also noted there were no adverse side-effects observed in the mice.
This mechanism similarly exists in other types of cancer and therefore the treatment could be valuable for use on those resistant to current therapies. The molecule PJ34 is being tested in pre-clinical trials according to FDA regulations before clinical trials begin.
Read more:
Five recent drug target discoveries for pancreatic cancer - Drug Target Review
- Oregon Stem Cell Treatment | Stem Cell Treatments [Last Updated On: August 22nd, 2014] [Originally Added On: August 22nd, 2014]
- oregon Stem Cell Clinic [Last Updated On: August 22nd, 2014] [Originally Added On: August 22nd, 2014]
- How to Volunteer for Clinical Stem Cell Research | eHow [Last Updated On: October 3rd, 2014] [Originally Added On: October 3rd, 2014]
- Oregon | Pet Stem Cell Therapy [Last Updated On: October 23rd, 2014] [Originally Added On: October 23rd, 2014]
- Arachnoiditis Stem Cell Treatment | eHow [Last Updated On: November 23rd, 2014] [Originally Added On: November 23rd, 2014]
- Obesity, high-fat diets during pregnancy could harm fetus [Last Updated On: December 30th, 2014] [Originally Added On: December 30th, 2014]
- Oregon Scientists Frustrated At Change In British Human Embryo Policy [Last Updated On: February 3rd, 2015] [Originally Added On: February 3rd, 2015]
- Stem cells definition of Stem cells in the Free Online ... [Last Updated On: February 17th, 2015] [Originally Added On: February 17th, 2015]
- OHSU research team successfully converts human skin cells ... [Last Updated On: October 19th, 2015] [Originally Added On: October 19th, 2015]
- Oregon Regenerative Medicine - Advanced Joint and Injury ... [Last Updated On: August 7th, 2016] [Originally Added On: August 7th, 2016]
- Oregon Stem Cell Center to focus on adult stem cells as ... [Last Updated On: November 20th, 2016] [Originally Added On: November 20th, 2016]
- News: VetStem Cell Therapy [Last Updated On: November 23rd, 2016] [Originally Added On: November 23rd, 2016]
- The Center for Traditional Medicine in Lake Oswego, Oregon [Last Updated On: November 23rd, 2016] [Originally Added On: November 23rd, 2016]
- Editing human embryos with CRISPR is moving ahead now's the ... - Phys.Org [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- Scientists genetically modify human embryos for first time, reports say - Medical Xpress [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- First safe repair of disease-causing gene in human embryos - Virginian-Pilot [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- Early gene-editing holds promise for preventing inherited diseases - The Jerusalem Post [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- Embryo Gene-Editing Experiment Reignites Ethical Debate - Scientific American [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- Meet the Oregon researcher whose embryo work is shaking the medical world - Portland Business Journal [Last Updated On: August 6th, 2017] [Originally Added On: August 6th, 2017]
- First embryo gene-repair holds promise for inherited disease - HollandSentinel.com [Last Updated On: August 14th, 2017] [Originally Added On: August 14th, 2017]
- Altering human heredity? Researchers repair disease-causing gene - TRT World [Last Updated On: August 17th, 2017] [Originally Added On: August 17th, 2017]
- The Public Needs to Weigh In on the Ethics of Genetically Engineering Humans - Slate Magazine [Last Updated On: August 17th, 2017] [Originally Added On: August 17th, 2017]
- Gene editing used to repair diseased genes in embryos - NHSUK - NHS Choices [Last Updated On: August 25th, 2017] [Originally Added On: August 25th, 2017]
- Stem Cells, Fetal Tissue Research & Cloning - Oregon Right ... [Last Updated On: August 25th, 2017] [Originally Added On: August 25th, 2017]
- New Biomedical Engineering Grants Aim at Heart Failure and Resistant High Blood Pressure - Newswise (press release) [Last Updated On: August 25th, 2017] [Originally Added On: August 25th, 2017]
- Stem Cells to Relieve Low Back Pain? WebMD [Last Updated On: October 14th, 2017] [Originally Added On: October 14th, 2017]
- Oregon Stem Cell Center Result of OHSU Research Strides ... [Last Updated On: July 26th, 2018] [Originally Added On: July 26th, 2018]
- Portland, Oregon Stem Cell Transplants, West Haven Sylvan ... [Last Updated On: August 18th, 2018] [Originally Added On: August 18th, 2018]
- Stem Cell Therapy Portland Oregon | Stem Cell Therapy [Last Updated On: September 2nd, 2018] [Originally Added On: September 2nd, 2018]
- Stem Cells | Medford | Ashland | Southern Oregon [Last Updated On: December 23rd, 2018] [Originally Added On: December 23rd, 2018]
- How A "Full Body Stem Cell Makeover" Works - Ben ... [Last Updated On: March 9th, 2019] [Originally Added On: March 9th, 2019]
- Stem rust - Wikipedia [Last Updated On: March 11th, 2019] [Originally Added On: March 11th, 2019]
- Inhibitory postsynaptic potential - Wikipedia [Last Updated On: April 3rd, 2019] [Originally Added On: April 3rd, 2019]
- What are stem cells? Oregon Light Therapy [Last Updated On: April 5th, 2019] [Originally Added On: April 5th, 2019]
- Adult Stem Cell Orthopedics - Oregon Regenerative Medicine [Last Updated On: April 5th, 2019] [Originally Added On: April 5th, 2019]
- PRP and Stem Cell Joint Regeneration | Portland Oregon [Last Updated On: April 5th, 2019] [Originally Added On: April 5th, 2019]
- Saccharomyces cerevisiae - Wikipedia [Last Updated On: May 13th, 2019] [Originally Added On: May 13th, 2019]
- About | OHSU [Last Updated On: September 7th, 2019] [Originally Added On: September 7th, 2019]
- Stem Cell Therapy Salem OR - oregonmedicalcenters.com [Last Updated On: September 7th, 2019] [Originally Added On: September 7th, 2019]
- Personalized Stem Cells, Inc. Announces First Patients Treated in FDA Approved Clinical Trial for Treatment of Osteoarthritis with Stem Cells - PR Web [Last Updated On: November 18th, 2019] [Originally Added On: November 18th, 2019]
- 2020 Emerging Scholars: Dr. Cathy Wong - Diverse: Issues in Higher Education [Last Updated On: February 6th, 2020] [Originally Added On: February 6th, 2020]
- 15 Good News Stories To Tackle The COVID-19 Sadness - IFLScience [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- Hospitals to Resume Elective Surgeries, Triggering a Surge in Blood Needs - southsoundtalk.com [Last Updated On: May 17th, 2020] [Originally Added On: May 17th, 2020]
- Oregon Medical Centers Regenerative Medicine ... [Last Updated On: July 4th, 2020] [Originally Added On: July 4th, 2020]
- Stem Cell & Regenerative Therapies | Oregon Regenerative ... [Last Updated On: July 4th, 2020] [Originally Added On: July 4th, 2020]
- STEM CELL THERAPY IN PORTLAND, OREGON - Cornell Pain Clinic [Last Updated On: July 4th, 2020] [Originally Added On: July 4th, 2020]
- Blood donors needed to keep blood supply stocked for local patients - The B-Town (Burien) Blog - The B-Town Blog [Last Updated On: October 16th, 2020] [Originally Added On: October 16th, 2020]
- 2017 Amtrak tragedy becomes call-to-action for Blood Donor Day this Sat., Dec. 18 - ilovekent.net [Last Updated On: December 18th, 2020] [Originally Added On: December 18th, 2020]
- YOUR HEALTH: Finding cures by tracking cells - WQAD.com [Last Updated On: July 21st, 2021] [Originally Added On: July 21st, 2021]
- Harvard study links exposure to wildfire smoke and COVID-19 with implications for BC - The Globe and Mail [Last Updated On: August 31st, 2021] [Originally Added On: August 31st, 2021]
- How to live longer: Green tea may halt brain decline and prolong life - Toys Matrix [Last Updated On: December 10th, 2021] [Originally Added On: December 10th, 2021]
- Gene Therapy for Hearing Loss on the Horizon : The Hearing Journal - LWW Journals [Last Updated On: January 5th, 2022] [Originally Added On: January 5th, 2022]
- Stem cell timeline: The history of a medical sensation ... [Last Updated On: January 5th, 2022] [Originally Added On: January 5th, 2022]
- Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their... [Last Updated On: May 15th, 2022] [Originally Added On: May 15th, 2022]
- Examining cooperation in nature: Q&A with author Kristin Ohlson - Mongabay.com [Last Updated On: September 25th, 2022] [Originally Added On: September 25th, 2022]
- Neuronal ceroid lipofuscinosis - Wikipedia [Last Updated On: November 16th, 2022] [Originally Added On: November 16th, 2022]
- Oregon baby undergoes fetal surgery for spina bifida | kgw.com [Last Updated On: November 24th, 2022] [Originally Added On: November 24th, 2022]