Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure the disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, researchers have discovered that the molecule CD44s seems to give cancer cells a survival advantage. In the lab, eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib. The study appears in the Proceedings of the National Academy of Sciences.
Treatment with erlotinib attempts to kill cancer cells by inhibiting EGFR signaling, a cellular mechanism that is hyperactive in most cases of glioblastoma multiforme and associated with poor prognosis, said senior author Dr. Chonghui Cheng, associate professor of molecular and human genetics and of molecular and cellular biology at Baylor College of Medicine. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance.
Erlotinib can inhibit EGFR signaling but in time cancer cells become resistant to the treatment, in part because other molecules can compensate for the lack of EGFR activity.
Increasing evidence also suggests that EGFR and related signaling mechanisms do not act alone. Another molecule present in a number of cancers, CD44s, seems to be involved in sustaining those cancer-promoting mechanisms, but how this happens remained a mystery.
CD44s gives cancer cells a survival advantage
In this study, we discovered a mechanism by which CD44s helps maintain the EGFR signaling activated in glioblastoma multiforme, said Cheng, who also is a professor in the Lester and Sue Smith Breast Center at Baylor, part of the NCI-designated Dan L Duncan Comprehensive Cancer Center. Working with a number of cancer cells grown in the lab, we determined that CD44s on the cell surface can enter the cell and prevent the digestion of EGFR, thus sustaining the activity of the signaling cascade that gives the cells a survival advantage.
Cheng and her colleagues have shown that CD44s holds a strategic place from which it can influence not only EGFR, but also a number of other signaling cascades that are important for cancer cell survival.
If we remove CD44s from the cell surface, we also can reduce the appearance of other molecules that could help cancer cells sustain their growth by compensating for the lack of EGFR activity, Cheng said.
Importantly from the therapeutic point of view, the researchers also found that removing CD44s from cancer cells in culture and treating them with erlotinib resulted in higher cancer cell deaths than treating with erlotinib alone. Cheng and colleagues anticipate that CD44s might also play a similar role in other types of cancer in which EGFR signaling is involved. This opens the possibility that targeting CD44s could potentially reduce the growth of many types of cancer, not just glioblastoma.
Researchers have been focused on developing inhibitors of EGRF and related pathways. Instead, we want to find novel approaches to boost the activity of inhibitors already available, and removing CD44s is a good example of how this could be done, said co-author Sali Liu, a graduate student in the Cheng lab. Our work suggests that in the future, physicians and scientists might approach cancer treatment in a different way. For example, instead of deciding on a treatment based on the type of breast cancer a patient has, they might choose a treatment according to the type of mechanism that helps this particular cancer grow, regardless of the type of cancer it is.
Other contributors to this work include Wei Wang, Honghong Zhang, Chung Kwon Kim, Yilin Xu, Lisa Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander Stegh and Shi-Yuan Cheng. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Northwestern University, Saitama Medical University and Kyorin University.
This research was supported in part by grants from the National Institutes of Health, the Northwestern University Brain Tumor Institute and a Brain Cancer Research Award from James S. McDonnell Foundation. Further support was provided by a Zell Scholarship at Northwestern University and the Cancer Prevention Research Institute of Texas.
Originally posted here:
How CD44s gives brain cancer survival advantage - Baylor College of Medicine News (press release)
- Podcast 9 Athens part 3 and news - November 8th, 2009 [November 8th, 2009]
- Podcast 10 Athens part 4 - November 8th, 2009 [November 8th, 2009]
- Podcast 11 Athens Part 5 - November 8th, 2009 [November 8th, 2009]
- Episode 12 Cardiac Nuclear Medicine in the UK - November 8th, 2009 [November 8th, 2009]
- Podcast 13 Choline PET and prostate cancer - November 8th, 2009 [November 8th, 2009]
- Episode14 ED function and Dysponea - November 8th, 2009 [November 8th, 2009]
- ep 15 Collimator Choice and Reconstruction algorithm - November 8th, 2009 [November 8th, 2009]
- Episode 16 Dr Strauss on vulnerable plaque - November 8th, 2009 [November 8th, 2009]
- Episode17 Chemical Stress - November 8th, 2009 [November 8th, 2009]
- Episode 18 Myocardial Perfusion Imaging and Diabetes - November 8th, 2009 [November 8th, 2009]
- Episode 19 The INSPIRE trial - November 8th, 2009 [November 8th, 2009]
- 20 Dual isotope with a difference - November 8th, 2009 [November 8th, 2009]
- Episode 21 The real effect of stress - November 8th, 2009 [November 8th, 2009]
- Episode 22 D-SPECT - November 8th, 2009 [November 8th, 2009]
- Episode 23 VQ Reprise - November 8th, 2009 [November 8th, 2009]
- Episode 24 Hepatobiliary Nuclear Medicine - November 8th, 2009 [November 8th, 2009]
- Episode 25 Sleep Apnea - November 8th, 2009 [November 8th, 2009]
- Episode 26 Imaging Post Traumatic Stress Disorder - November 8th, 2009 [November 8th, 2009]
- Episode 27 Cardiac Stem Cells - November 8th, 2009 [November 8th, 2009]
- Episode 28 Molly Supply - November 8th, 2009 [November 8th, 2009]
- Episode 29 Melanoma therapy interview with Dr Ekaterina Dadachova - November 8th, 2009 [November 8th, 2009]
- Episode 30 Viral Therapy - November 8th, 2009 [November 8th, 2009]
- Episode 31 breast radiotherapy using radioisotopes - November 8th, 2009 [November 8th, 2009]
- Episode 32 news from snm - November 8th, 2009 [November 8th, 2009]
- Episode 33 EBV Imaging and Therapy - November 8th, 2009 [November 8th, 2009]
- Episode 34 Dr Lele SNM India 2009 - December 14th, 2009 [December 14th, 2009]
- Episode 35 Dr Andrew Scott from the Ludwig institute - January 10th, 2010 [January 10th, 2010]
- Episode 36 CardiArc - February 25th, 2010 [February 25th, 2010]
- Episode 37 Dr Modder Radiosynoviorthesis (Radiation Synovectomy) - March 31st, 2010 [March 31st, 2010]
- Episode 38 Indian Nuclear Medicine With Dr Malhotra and Dr Krishna - May 28th, 2010 [May 28th, 2010]
- Episode 39 Prof Ora Israel The Utility of Hybrid Imaging - July 13th, 2010 [July 13th, 2010]
- Episode 40 New V/Q SPECT developments - October 11th, 2010 [October 11th, 2010]
- Episode 41 scintimun - February 14th, 2011 [February 14th, 2011]
- Episode 42 Radio-Isotope Supply into the future - March 6th, 2011 [March 6th, 2011]
- Podcast 4: DNA therapy - April 24th, 2011 [April 24th, 2011]
- Sorry about the delay a new podcast will be out soon! - April 24th, 2011 [April 24th, 2011]
- Podcast 5 Flash 3D - April 24th, 2011 [April 24th, 2011]
- Podcast 6 Affibody - April 24th, 2011 [April 24th, 2011]
- Podcast 7 EANM 2006 Athens Part 1 - April 24th, 2011 [April 24th, 2011]
- Podcast 8 Athens Part 2 - April 24th, 2011 [April 24th, 2011]
- Episode 43 Rapidscan Part 1, 720P high quality video version - May 1st, 2011 [May 1st, 2011]
- Episode 43 Rapidscan Part 1, Ipod quality video - May 1st, 2011 [May 1st, 2011]
- Episode 43 Rapidscan Part 1, Audio version - May 1st, 2011 [May 1st, 2011]
- Episode 45 Mummies with cardiovascular disease video - May 21st, 2011 [May 21st, 2011]
- Episode 45 Mummies with cardiovascular disease audio edition - May 21st, 2011 [May 21st, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective - August 7th, 2011 [August 7th, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective audio version - August 7th, 2011 [August 7th, 2011]
- Episode 47 Cardiac Image Fusion With Dr Kaufmann - September 18th, 2011 [September 18th, 2011]
- Episode 47 Cardiac Fusion with Dr Kaufmann video version - September 18th, 2011 [September 18th, 2011]
- Dear Steve, I am and many more like me are your one more thing. - October 9th, 2011 [October 9th, 2011]
- EPISODE 48 PET MRI camera from Siemens with Dr Georgi audio - October 23rd, 2011 [October 23rd, 2011]
- EPISODE 48 PET MRI camera from Siemens Dr Georgi video - October 23rd, 2011 [October 23rd, 2011]
- Silicon Biosystems to Present Single-Circulating Tumor Cell Molecular Characterization at the Fourth World CTC Summit - April 25th, 2012 [April 25th, 2012]
- Leukaemia cells have a remembrance of things past - April 25th, 2012 [April 25th, 2012]
- Technologist Education Requirements Can Help Cut Repeat Scans - April 25th, 2012 [April 25th, 2012]
- HKU Collaborative Research Discovers A Novel Molecular Mechanism Of A New Anti-HIV-1 Drug Candidate - April 25th, 2012 [April 25th, 2012]
- Focal Segmental Glomerulosclerosis and the Nephrotic Syndrome - Part 1 Clinical - Video - May 4th, 2012 [May 4th, 2012]
- Electro-Medicine : Biological Physics - The Molecular Basis of Alzheimers Disease - Video - May 4th, 2012 [May 4th, 2012]
- osdd heterocyclic compounds and molecular medicines - Video - May 4th, 2012 [May 4th, 2012]
- Molecule to Medicine: The Biomarker Frontier - Video - May 4th, 2012 [May 4th, 2012]
- Fulfilling the Promise of Molecular Medicine in a Developmental Brain Disorder - Video - May 4th, 2012 [May 4th, 2012]
- Focus on Stefanie Dimmeler - Video - May 4th, 2012 [May 4th, 2012]
- Dundee - May 4th, 2012 [May 4th, 2012]
- Nanotechnology In Medicine: Huge Potential, But What Are The Risks? - May 5th, 2012 [May 5th, 2012]
- Cutting Edge Technology Coming To DMH - May 5th, 2012 [May 5th, 2012]
- This Week in Experimental and Molecular Pathology - May 5th, 2012 [May 5th, 2012]
- Researchers' discovery offers hope for cancer, heart disease miracle drugs - May 7th, 2012 [May 7th, 2012]
- Penn State student Zachary Hostetler from Garnet Valley is being honored as a student marshal - May 7th, 2012 [May 7th, 2012]
- NCKU Student Wins Prestigious Award for Anti-Cancer Research - May 10th, 2012 [May 10th, 2012]
- In-Vitro Diagnostics (IVD) Market (Clinical Chemistry, Immunoassays, Molecular Diagnostics, Hematology Analyzers ... - May 10th, 2012 [May 10th, 2012]
- Pitt team uses genomics to identify a molecular-based treatment for a viral skin cancer - May 10th, 2012 [May 10th, 2012]
- Genomics used to identify a molecular-based treatment for a viral skin cancer - May 10th, 2012 [May 10th, 2012]
- 2 molecular biologists get $500K medical prize - May 13th, 2012 [May 13th, 2012]
- 2 molecular biologists share $500K medical prize - May 13th, 2012 [May 13th, 2012]
- Lab21 Unveils New Molecular Analysis Services at Greenville Site - May 13th, 2012 [May 13th, 2012]
- 2 molecular biologists from NYC to share $500K medical prize for pioneering research on cells - May 13th, 2012 [May 13th, 2012]
- Two Molecular Biologists Get $500K Medical Prize - May 13th, 2012 [May 13th, 2012]
- Pair of molecular biologists receive Albany Medical Center Prize - May 13th, 2012 [May 13th, 2012]
- CNIO scientists successfully test the first gene therapy against aging-associated decline - May 16th, 2012 [May 16th, 2012]
- Cancer Institute of New Jersey Aims to Advance Personalized Cancer Treatments Through 'Precision Medicine' - May 16th, 2012 [May 16th, 2012]