I’m encouraged, first, by the rapidity of these drugs’ emergence: ten years ago, none of the kinase-blocking drugs were available except for a few in experimental trials; most received FDA approval only in the past five years. These are very new agents indeed.
Why I’m enthusiastic – I anticipate that within a few years from now, cancer patients will take “medication cocktails” for their tumors, much in the way people living with HIV use drug combinations to fend off infection. Cancer will, in many circumstances now deemed incurable, be managed instead as a chronic disease.
Now I can complete my assignment – a list of current, oral FDA-approved targeted cancer therapies. As indicated previously, I’m not including hormonal treatments in this list. I considered oral drugs targeting kinases in the last post.
I should emphasize that I’m neither recommending nor advocating any particular drugs. Rather, my point is to demonstrate the evolution of the field, that so many new and varied types of cancer pills are available. I think this is the start of a new era in oncology with expanded treatment options for people with all kinds of malignancy.
1. Zolinza (vorinostat) is FDA-approved for use in a few forms of lymphoma that are cutaneous T cell lymphoma (CTCL). These are non-Hodgkin’s lymphomas in which the malignant cells are T-lymphocytes infiltrating the skin.
How this agent works is by inhibiting histone deacetyalases. These enzymes act in the cell’s nucleus, or center, where lies the DNA strung out along chromosomes. It removes acetyl groups, small chemical structures, from histone proteins. The genetic material normally wraps around the histones, and the presence or absence of acetyl groups on histones affects how genes are turned on or off. (Merck, October 2006).
2. Targretin (bexarotene) comes in capsule and in gel forms. It’s a retinoid, a Vitamin A-like compound that binds retinoid X receptors. These receptors regulate gene expression in normal and malignant cells. The drug is FDA-approved for use in CTCL. (Ligand, now Eisai, December 1999).
3. Vesanoid (tretinoin) is a retinoid that binds retinoic acid receptors. This drug is approved by the FDA as part of the treatment regimen for a particular form of leukemia called acute promyelocytic leukemia (APL). The drug targets a retinoic acid receptor that’s abnormally produced in the malignant cells due to a disease-defining chromosomal switch involving the retinoic acid receptor alpha (Roche, and generic, 1995)
This list is derived, in part, from information on the National Cancer Institute website on targeted cancer therapies, supplemented by other public-access resources on the relevant drugs and molecules as I’ve indicated with relevant links.
In this review, I note that some drugs that are not conceptually distinct from conventional chemotherapy or hormonal treatment appear to be marketed as “targeted” cancer treatment. My concern is that some companies are using this term, which implies a scalpel-like effectiveness and selectivity, to sell drugs to patients and oncologists (who may not all be up on their kinases) regardless of the drugs’ real specificity or lack thereof.
Given that all cancer drugs are designed, in principle, to kill malignant cells without killing the person who has cancer, we might consider all anti-tumor drugs as “targeted therapy.” But I don’t think that would be reasonable or helpful to patients and physicians who are trying to distinguish among treatment options.
In my opinion, the “targeted” term should apply only to drugs that impede troublesome molecules that act up particularly in the malignant cells, such as the bcr-abl tyrosine kinase mentioned in the last post, or the altered retinoic acid receptor that’s implicated in APL, as considered above.