A team of University of Michigan researchers is developing a new anti-cancer drug that is absorbed through the guts lymphatic system rather than blood vessels, potentially outmaneuvering the molecular signaling pathways that lead to drug resistance while increasing cancer-fighting ability and reducing side effects.
In a study published today inNature Communications,the team reports on a novel kinase inhibitor that significantly reduced disease, limited toxicity and prolonged survival in mice with myelofibrosis, a precursor to acute leukemia.
SEE ALSO: Researchers find link between genetic mutations and cancer treatment resistance
They designed the oral medication LP-182 to simultaneously target phosphoinositide 3-kinase, also known as PI3K, and mitogen-activated protein kinase, known as MAPK, molecular signaling pathways that drive a high percentage of cancers.
MORE FROM THE LAB: Subscribe to our weekly newsletter
Cancer treatment often involves combination therapy to target different cancer cell vulnerabilities. But because these drugs circulate through and are absorbed and removed by the body at different rates, it can be challenging to sustain the right therapeutic balance of each individual drug at a concentration necessary to be effective while limiting drug toxicity and side effects, said lead authorBrian D. Ross, Ph.D., the Roger A. Berg Research Professor of Radiology at the University of Michigan Medical School.
Failure to strike this balance reduces the effectiveness of the drug combinations against cancer and can lead to drug resistance, as PI3K and MAPK crosstalk can activate downstream pathways to resist therapy. Even if a drug blocks one pathway, another can provide an escape survival pathway to compensate and continue growing.
Like Podcasts? Add the Michigan Medicine News Break on Spotify, Apple Podcasts or anywhere you listen to podcasts.
Unlike traditional oral drugs, which are often designed to be rapidly absorbed into the bloodstream, researchers treating mice with myelofibrosis found that LP-182 is absorbed by the guts lymphatic system first. The lymphatic system serves as a storage reservoir, separating the drug from the rest of the body and gradually releasing the therapy into the general circulation over time to maintain drug concentrations at an optimal therapeutic level.
SEE ALSO: Study Suggests New Approach to Improve Radiation Therapy Resistance in Glioblastoma
Within the therapeutic window, we are able to maintain the on-target inhibition of two distinct pathways that are talking to one another, said Ross, who is also the director of the Center for Molecular Imaging at Michigan Medicine and director of the Preclinical Molecular Imaging Shared Resource at the U-M Rogel Cancer Center. This demonstrates the feasibility of delivering anti-cancer agents directly into the lymphatic system, which opens tremendous new opportunity for improving cancer therapeutic outcomes and reducing the side effects of the agents themselves.
In myelofibrosis, excessive scar tissue forms in the bone marrow, disrupting normal blood cell production. Overactive molecular signaling leads to a proliferation of malignant stem cells, extensive fibrosis, enlarged spleen and progressive bone marrow failure.
See more here:
New drug candidate uses novel absorption method to target cancer cells in mice - Michigan Medicine
- Jianping Fu Mechanical Engineering - University of Michigan - July 11th, 2022
- Cell Culture Market Key Drives Zeroing In On The Main Merchants | Danaher Corporation, Thermo Fisher Scientific Designer Women - Designer Women - July 11th, 2022
- Erasing The Stigma Of Sickle Cell Disease Through Advocacy - Essence - June 22nd, 2022
- This One Group Of People Holds The Key To Staying Young, Study Says Eat This Not That - Eat This, Not That - May 2nd, 2022
- Primary Cells Market 2022 is set to experience a significant growth rate | PromoCell GmbH, HemaCare Corporation, Thermo Fisher Scientific ... - May 2nd, 2022
- 3D Cell Culture Market to 2030 | Industry Statistics, Emerging Demands, Forecast to 2030 | 3D Biotek, LLC Advanced Biomatrix, Inc. Becton, Dickinson... - May 2nd, 2022
- Oral Cavity | histology - University of Michigan - April 19th, 2022
- Unraveling Stem Cells' Secrets: Immortality of Germline Cells and the Function of Junk DNA - SciTechDaily - April 19th, 2022
- Scientists De-Aged a Woman's Skin Cells by 30 Years - The Daily Beast - April 19th, 2022
- Longboat residents recall the greatest gifts - YourObserver.com - December 24th, 2021
- Nebraska Athletics News: Recruiting Season, Living Robots and Stuck in IKEA - Corn Nation - December 10th, 2021
- Duke Faculty Promoted or Appointed to the Rank of Full Professor - Duke Today - November 8th, 2021
- Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living - November 8th, 2021
- Male Infertility Could Be Treated With Monkey Cells; New Study Shows How These Animals Could Help Address the Condition - Science Times - October 28th, 2021
- Insights & Outcomes: Place cells, planarians, and 'prewet' proteins - Yale News - October 28th, 2021
- Using a mini heart model to develop new therapies - MSUToday - October 5th, 2021
- Rowan University hosts National Science Foundation research program for undergrads - Rowan Today - August 31st, 2021
- Loss of a top autism gene may alter neuron structure - Spectrum - January 17th, 2021
- Rogel team receives $11.2M to leverage the microbiome against GVHD - Newswise - October 28th, 2020
- Latest Update 2020: What Are the Key Players Evolving In the Growth of the 3D Cell Culture Market? - re:Jerusalem - October 28th, 2020
- Listings - CON, THE on ABC | TheFutonCritic.com - The Futon Critic - October 15th, 2020
- ABC News Debuts New Primetime Series THE CON Narrated by Whoopi Goldberg - Broadway World - October 8th, 2020
- HOME GROWN: Pumpkins best left on the vine for as long as possible - The Oakland Press - October 8th, 2020
- Official Missteps in Michigan's Worst Covid Prison Outbreak - The Intercept - September 29th, 2020
- Regenerative medicine and war: The next breakthrough in treating injured veterans? - Genetic Literacy Project - September 29th, 2020
- Hematopoietic Stem Cells (HSCs) Market Primary Research, Secondary Research, Product Research, Trends And Forecast By 2026- Kite Pharma Inc., Thermo... - September 29th, 2020
- New research connects the hormones we're born with to lifetime risk for immunological diseases - MSUToday - September 20th, 2020
- School of Science grows by 10 - MIT News - September 10th, 2020
- COVID-19 Drug Discovery and Development Why Diverse Strategies Are Critical - Technology Networks - September 10th, 2020
- Researchers identify environmental components that affect gene expression in cardiovascular disease - The South End - June 21st, 2020
- Hesperos Human-on-a-Chip used to model Alzheimer's and MCI - SelectScience - June 2nd, 2020
- Are immune-compromised kids at greater risk from Covid-19? - Health24 - May 3rd, 2020
- Erika Hersch-Green Wins CAREER Award for Biodiversity Research - Michigan Tech News - May 2nd, 2020
- Science Becomes A Dividing Issue In Year Of Election And Pandemic - Michigan Radio - May 2nd, 2020
- In a CRISPR first, Editas therapy used to fix genes in the body - BioPharma Dive - March 11th, 2020
- Stopping Smoking Allows Healthy Lung Cells to Proliferate - Medscape - February 8th, 2020
- After a bone injury, shape-shifting cells rush to the rescue - University of Michigan News - January 29th, 2020
- Engineer the future of human health with a PhD in biomedical engineering - Study International News - January 29th, 2020
- The Unexpected Diversity of Pain - Scientific American - January 24th, 2020
- BREAKING: A woman gives birth to the Son of God (Part II) - INQUIRER.net - January 5th, 2020
- Collaborative Robots: Rai... - Robotics Online - December 19th, 2019
- VetStem Biopharma Shares the Success Story of Jesse Who was Treated with VetStem Cell Therapy - PR Web - December 8th, 2019
- Stem Cell Therapy Michigan | Regenerative Medicine 248-216 ... - February 27th, 2019
- Stem Cell Treatments Bloomfield Hills, MI | 248-216-1008 - January 9th, 2019
- Michigan Integrative Health Dr. Roy Picard, D.C. - December 27th, 2018
- Breast Cancer Stem Cells Stopping Them In Their Tracks ... - November 23rd, 2018
- Stem Cell Treatments MI | Michigan Center for Renerative ... - November 2nd, 2018
- Michigan Stem Cell Therapy - Foot HealthCare Associates - November 2nd, 2018
- Cancer Stem Cell Research | University of Michigan Rogel ... - November 2nd, 2018
- University of Michigan Stem Cell Research | Treatment and ... - November 2nd, 2018
- Detroit Michigan Stem Cell Therapy - americanregen.com - September 28th, 2018
- Combination of traditional chemotherapy, new drug kills ... - September 4th, 2018
- Stem Cells FAQ Michigan Stem Cell Institute - August 29th, 2018
- Anti-Aging, Regeneration and Stem Cell Supplements - August 7th, 2018
- Families raise money for research into rare diseases - KARE - September 8th, 2017
- Cells that stand in the way of HIV cure: Discovery expands understanding of marrow's role - Medical Xpress - August 5th, 2017
- Turmeric and black pepper fight cancer stem cells - November 26th, 2016
- Michigan company mines stem cells in search of Fountain of ... - November 18th, 2016
- stem cell research | Michigan Radio - October 6th, 2016
- Stem Cell Therapy Treatment at Allure Medical Spa in Michigan - October 6th, 2016
- University of Michigan Stem Cell Research | Experts List - September 20th, 2016
- Five years after Michigan vote on human embryonic stem ... - August 26th, 2016
- Scientists coax stem cells to form 3-D mini lungs ... - August 11th, 2016
- Cancer stem cells - University of Michigan Comprehensive ... - July 25th, 2016
- Michigan Catholic Conference: Home - October 19th, 2015
- Michigan Stem Cell Amendment, Proposal 2 (2008 ... - July 2nd, 2015
- University of Michigan Stem Cell Research | Embryo Donation - May 12th, 2015
- University of Michigan Stem Cell Research | Stem Cell ... - April 22nd, 2015
- How to grow a human lung - March 25th, 2015
- Novogen (NVGN) Promising Data in Brain Cancer; eFuture Information Technology (EFUT) and ... - March 5th, 2015
- Stem Cell Research - Right to Life of Michigan - February 24th, 2015
- Breast Cancer Stem Cell Research - University of Michigan ... - January 17th, 2015
- What makes pancreatic cancer so aggressive? New study sheds light - January 16th, 2015
- Leukemia Stem Cell Research | University of Michigan ... - January 4th, 2015
- Seeing Is Believing - December 12th, 2014
- Swiston receives Commitment to Education Award - November 29th, 2014
- Bone marrow registration drive to be held at Saint Mary's College - November 18th, 2014
- Researchers devise a means for growing near 2-D chemical gardens (w/ Video) - November 11th, 2014
- Stem cells help doctors restore womans smile, regenerating bone to hold dental implants - November 5th, 2014
- Reason to Bree-Lieve: Greenville girl continues to beat the odds - November 5th, 2014