TWiPO #19 ~ More on Hedgehog signaling, brain tumor risk from cell phone use, and FDA approval of cancer drugs

October
30, 2011Several just-published papers in the literature
relate to recent podcast episodes, and host Dr. Tim Cripe and co-host Dr.  Lionel Chow review these interesting
developments.
0:55 Hedgehog Signaling: Recent papers
discussing this pathway in neuroblastoma and rhabdomyosarcoma are discussed,
with implications for treatment in these tumor types with itraconozole.
6:40 Cell phone and brain tumor risk: The
controversy concerning criticism by the Environmental Health Trust of a study
showing that cell phone use does not increase risk of brain tumors in children
is explored.
Accelerated approval of cancer drugs by the FDA
and implications for pediatric cancers.
15:30 Brentuximab for two types of lymphoma
21:20 Vemurafenib for melanoma
28:30 Crizotinib for non-small cell lung cancer
(and potential use in neuroblastoma)
42:30 Response to email regarding personalized
medicine TWiPO episode #17 and lab blog for Dr Charles Keller at OHSU
References:
Pediatr Blood Cancer. 2011 Dec 1;57(6):930-8.
doi: 10.1002/pbc.23174. Hedgehog pathway activity in
pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: a report
from the Children's Oncology Group.
Int J Oncol. 2011 Oct;39(4):899-906. doi:
10.3892/ijo.2011.1076. Pharmacological inhibition of
the Hedgehog pathway preventshuman rhabdomyosarcoma cell growth.
Cancer Lett. 2011 Nov 28;310(2):222-31. Inhibition of the sonic hedgehog
pathway by cyplopaminereduces the CD133+/CD15+ cell compartment and the in
vitrotumorigenic capability of neuroblastoma cells.
Cell Phone Study Was Flawed, Say Some Experts by
Roxanne Nelson Medscape Oncology News.
The JNCI Study by Aydin et al on Risk of Childhood Brain Cancer from
Cellphone Use Reveals Serious Health Problems, Environmental Health Trust.
N Engl J Med. 2010 Nov 4;363(19):1812-21. Brentuximab
vedotin (SGN-35) for relapsed CD30-positive lymphomas.
FDA Approves Brentuximab for Two Lymphomas By:
ELIZABETH MECHCATIE, Oncology Report Digital Network.
Clin Cancer Res. 2011 Oct
15;17(20):6428-36. Brentuximab Vedotin (SGN-35).
FDA Approves Vemurafenib for Advanced Melanoma.
By: JANE SALODOF MACNEIL, Oncology Report Digital Network.
N Engl J Med. 2011 Jun
30;364(26):2507-16. Improved survival with
vemurafenib in melanoma with BRAFV600E mutation.
N Engl J Med. 2011 Jun 30;364(26):2547-8. Been
there, not done that--melanoma in the age of molecular therapy. http://www.ncbi.nlm.nih.gov/pubmed/21639809
Biochem J. 2011 Aug 15. Activating ALK mutations found in neuroblastoma are inhibited by
Crizotinib and NVP-TAE684.
N Engl J Med. 2010 Oct
28;363(18):1693-703. Anaplastic lymphoma kinase inhibition in non-small-cell
lung cancer.
Nature. 2007 Aug 2;448(7153):561-6. Epub 2007
Jul 11. Identification of the transforming EML4-ALK fusion gene in non-small-cell
lung cancer.
Science. 1994 Mar 4;263(5151):1281-4. Fusion of a kinase gene, ALK, to
a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.

TWiPO #17 ~ Personalized medicine: Interview with Dr Giselle Sholler

October
13, 2011
Host Dr. Tim Cripe and co-hosts Dr. Lars Wagner
and Dr. Lionel Chow welcome guest Dr. Giselle Sholler on this episode of TWiPO.
Dr. Sholler gives the background to her current research interest in
neuroblastoma, and describes her nifurtimox trials and how she formed the
Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC).
The physicians also discuss the specifics of the personalized medicine
feasibility trial now open for neuroblastoma.
Dr. Sholler is a Pediatric Oncologist with
Spectrum Health Medical Group, Helen DeVos Childrens Hospital, and directs the
Pediatric Oncology Therapeutic Discovery Clinic. She is also Co-Director of the
VARI/TGen Pediatric Oncology Research Program, and Associate Professor of the
Neuroblastoma Translational Research Laboratory at Van Andel Research
Institute. She has a faculty appointment within Michigan State University's
College of Human Medicine, and continues as adjunct faculty at University of
Vermont. Dr. Sholler is also a Guest Researcher in the Pediatric Oncology Branch
at the NCI.
References:
J Clin Oncol. 2010 Nov 20;28(33):4877-83. Epub
2010 Oct 4. Pilot study using molecular profiling of patients' tumors to find
potential targets and select treatments for their refractory cancers.
Science 16 Sept 2011: Vol. 333 no. 6049 pp.
1569-1571. Pushing the Envelope in Neuroblastoma Therapy
Mol Cancer Ther August 2011 10; 1311. A Pilot
Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with
Advanced Cancer

TWiPO #14 ~ Interview with Dr Kate Matthay

August
24, 2011
In this enlightening interview with Dr. Kate
Matthay, a reknown leader in the neuroblastoma research community, host Dr. Tim
Cripe draws out the inspiration for her early interest in medicine and why her
career grew with a focus on neuroblastoma. Dr. Matthay explains the history and
challenges of clinical research for neuroblastoma:
10:00 challenges in planning and conducting the
CCG-3891 double randomized trial questioning the need for transplant and
cis-retinoic acid
15:00 discussion of the COG-A3973 trial
questioning the need for purged stem cells
15:50 rationale for the COG-ANBL0532 single
versus tandem transplant trial
16:13 discussion of the COG-ANBL0032 ch14.18
with cytokines trial
18:00 MIBG COG pilot trial
22:00 work with SIOP and NB protocol
development for children in Morocco (N Africa)
Please send any questions or comments to
twipo@solvingkidscancer.org

TWiPO #3 ~ Vincristine Pharmacogenetics, Irinotecan/Temozolomide for Relapsed Neuroblastoma

April
25, 2011
In this third episode, host Tim Cripe, MD, PhD,
asks his co-hosts to discuss two recent papers that provide new information
about genetic predisposition to increased toxicity to vincristine in some
children, and the results of a phase II study using a combination therapy
(irinotecan and temozolomide) in relapsed or refractory neuroblastoma.
1:24 Maureen
O'Brien, MD discusses "Increased risk of vincristine neurotoxicity
associated with low CYP3A5 expression genotype in children with acute
lymphoblastic leukemia" in Pediatr Blood Cancer. 2011 Mar;56(3):361-7.
doi: 10.1002/pbc.22845. Epub 2010 Nov 11.http://www.ncbi.nlm.nih.gov/pubmed/21225912
22:10 Lars
Wagner, MD discusses "Phase II study of irinotecan and temozolomide in
children with relapsed or refractory neuroblastoma: a Children's Oncology Group
study" from J Clin Oncol. 2011 Jan 10;29(2):208-13. Epub 2010 Nov
29. http://www.ncbi.nlm.nih.gov/pubmed/21115869