Hello Maurice. I figured it was about time to wake up Idec shareholders as to other cancer treatments, including NHL (funny the Idec 10 K never mentions Techniclone). To IDPH shareholders, Golfdad is a Yahoo! poster on the TCLN thread and an employee of Texas Medical Center. Enjoy.
Cancer biology comments golfdad97
(55/M/Houston TX) Aug 7 1998
9:48AM EDT
This is going to be a long post, my apologies in advance. But I think my comments will be relevant to the posters on this board. The phrase "cancer cure" is starting to appear more frequently on posts...and while that's what this business is all about, please allow me to soften the implications of the innovative techniques being championed by TCLN. Without a long review of fundamental cancer biology (that would give Biotex fits), let me work up to a couple of points about TNT and Oncoylym-mediated therapy. In general, a malignant diagnosis means that the cells examined by the pathologist upon biopsy have an abnormal morphology (appearance) and are invading the surrounding normal tissue. This invasion is the hallmark of malignancy, since it predisposes the tumor population present at that site to gain entrance into the lymphatics and blood circulation which can eventually result in metastasis to distant organs. The process of metastasis and subsequent therapy of these metastases (about which I have written several review articles) is the target of drug-company R&D today...that is, can one prevent metastasis or target metastases that are either occult (hidden, we know that they are there in a certain percentage of patients, depending upon the staging of the cancer at the time of diagnosis) or have manifested themselves in symptoms and perhaps are visible my imaging techniques. Trust me, I'll get to the point. Cure? Well, take an example, say, a malignant primary tumor in the wall of the colon that has not invaded the connective and muscular tissue of the colon wall and is not found is associated lymphatics is a good candidate to be cured by surgery. Basal cell carcinomas (old folks faces) is rarely metastatic, can be cured by excision most all of the time. Anyway, the cure rate is extremely high for this colon cancer circumstance. However, in many of the cases of common solid tumors, such as colon, breast, renal cell, lung, melanoma and prostate...when the initial examination shows that lymphatic nodes that drain the local tumor are postive (or perhaps the PSA remains elevated after prostatectomy as an example), or scans with isotopes known to localize in regions of metastatic tumor are positive, or just plain statistical knowledge of the disease staging indicates that there will be the emergence of metastatic disease (in predictable sites), the therapy is now directed to the therapy of metastasis. I have mentioned several times that this is the name of the game (will not comment on TNT-mediated therapy of primary gliomas). Now this is where the term "cure" becomes very problematic...because you are dealing with a distribution of tumor cells throughout organs which are being selcted on an individual basis (we are not all alike in how we interact with our tumors, even if 100 patients have the exact same diagnosis; the phrase I helped coin over the years is "tumor-host relationship"). We confound that problem by intervention with therapies that further select for abberant subpopulations of tumor cells (we especially do that with the use of biological response modifiers which are plentiful in use in clinical trials). More (think I can keep it to two posts)
The primary tumor and its metastases contain subpopulations of cells that continue to evolve and mutate (my standard line), so not only are we faced with ineffective therapy due to the site of where the tumors have emerged, but we also confront tumor cells that have upregulated their own metabolic pathways that circumvent targeted therapy. Examples include multiple pathways that inactivate and pump out toxic drugs, downregulate (no longer express) target molecules such as growth factor receptors or unique antigens, or a myriad of cell-surface molecules, perhaps like lym-1, CD20, CD40, Fas, etc, etc. In addition, mutations include the increase of intracellular survival factors for the cells (such as a host of oncogene products which I won't list). The point is, these tumors are at the present time, untreatable. Enter Techniclone. As I have stated many times in the past, TNT-mediated delivery targets molecues that rarely, if ever, mutate (those DNA histones) and we now have a chance to make the "target stand still for a moment", while we deliver goodies that are going to kill it...and we change the destiny of therapy for these localized, bulky metastases that would normally become nonresponsive and kill the patients. We can deliver substances that will change the tumor microenvironment. We can deliver toxic agents. We can change the permeability of the tumor capillary bed, or perhaps wipe out the blood supply. We move from an era of no effective therapy to one that now says, for the first time in two decades, maybe we can dramatically alter the prognosis for these patients. Cure? Don't know. Doubt it. The cancer remains too smart, the biology too tough...but it's a damn good start...the lifespan and outlook is dramatically improved and its a breakthrough. I'll settle for that for now. BobLLL and M. Winn on SI give two excellent posts about oncolym, rituxan and bexxar regarding the targeting of different antigens on lymphoma cells. I agree with Winn completely that I would rather take on 10,000 cells with multiple antibodies than wait for the emergence of 100 million cells months later that have changed on me...and BobLLL is quite correct and articulate about the dependence of cell-type and affinity and expression of binding sites on varying types of lymphoma, especially since low-grade is primarily a B-cell phenotype. In my opinion, ultimate cures will come from intimate knowledge about the tumor-host relationship for individual patients and knowlege of how we target certain properties of their tumor. TNT offers new hope, a new technology that is so very widespread in its applications in the everyday therapy of cancer, I consider it a new beginning. We are a part of that. Okay, I used up a week's aliquot of posts. Blessings to all of the families here that are devoured by this satanic disease.
golfdad97
<golfdad teaches at Texas Medical Center. The posts golfdad refers to are from you and Bob L on SI TCLN thread, #s 2394 &2396.> |
