Like pancreatic cancer, lung cancer is another notoriously difficult cancer to treat. Admittedly, I am slightly ripping off 'mtaotters' Sept. 17, 2013 2:14 PM novel idea regarding HA accumulation and diabetes.
I am wondering if a similar HA like barrier exists in lung cancer patients whereby ECM buildup prevents drug perfusion to lung cancer cells. I'm thinking more along the lines of long term HALO benefit if it were ever to be acquired.
NOTE: The Fezziwig side of Fezz-fgnoms will hate this idea because she didn't think of it first (See her Sep 17, 2013 7:51 PM reply to 'mtaotter's initial brilliant post a week ago about HA accumulation and diabetes). And yes, fezzfgnoms, I know clinical trials are expensive.
Reference to get a PEGPH20 Lung cancer discussion started:
#1. Respir Investig. 2013 Jun;51(2):92-7. doi: 10.1016/j.resinv.2013.02.002. Epub 2013 Mar 19.
Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma.
#2. Clin Exp Metastasis. 2013 Jun;30(5):595-606. doi: 10.1007/s10585-012-9563-4. Epub 2013 Jan 4.
Hyaluronan synthesis inhibitor supplements the inhibitory effects of zoledronic acid on bone metastasis of lung cancer.
#3. Clin Immunol. 2013 Jan;146(1):56-69. doi: 10.1016/j.clim.2012.11.002. Epub 2012 Nov 14.
The role of hyaluronic acid in SEB-induced acute lung inflammation.
#4. J Biol Chem. 2013 Jan 4;288(1):520-8. doi: 10.1074/jbc.M112.393629. Epub 2012 Nov 21.
Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction.
Lastly, from 2013 10-K. Afriendofthedevil (below) has articulated this fact quite nicely below. Thanks again afriendofthedevil...
"Overall, approximately 25 percent of solid malignancies accumulate high levels of HA, including pancreatic, **lung**, breast, colon and prostate cancers, and therefore we believe that PEGPH20 has the potential to help patients in these types of cancer."
You know that pancreatic mets to the lung is different from NSCLC, right? But your point is well taken. What makes the PegpH20 drug potentially so exciting is how it could completely change the landscape of chemotherapy for many cancers. If it does well for pancreas cancer, watch out for a quick dozen or more partnerships with different companies for their chemo drugs in a variety of cancers.
So . . . despite being chided by the great, all-knowing fezzgnoms (see "Imbecile Samson ISIS- Lung CA is not on High Hyaluron List" Sept. 19. 2013), it DOES appear HALO is interested in the lung cancer indication for PEG-PH20.
I think the curtain of the Wizard of Oz has just been pulled back a bit - he's human afterall... Go HALO.
From HALO Q2 2013 CC :
Q: “And second question, as you think about other solid tumors, is there obvious go-to solid tumor next, which has high levels of hyaluronan or are you going to be serving tumors looking for subsets of patients that have high levels of hyaluronan?
A: “ . . . we've really spent a lot of time being kind of disciplined as far as surveying the landscape, starting with the biopsies and really understanding the disease and looking for those where the biology supports it. . . . The second, of course, is this context of things is bronchogenic non-small cell lung carcinoma.”