A New Age in Cancer Treatment – Part I

By Mordechai Applebaum

Mordechai Applebaum

Israel’s Drug Panel announced the list of approved medical treatments that will receive federal subsidies for 2017 [1]. Interestingly, half of the 510M NIS budget has been dedicated for treating cancer. This might not be surprising given the unfortunate pervasiveness of the disease. But why is cancer so rampant and its cure so elusive even 45 years after The National Cancer Act of 1971 and the “war on cancer” that has be waged? Are we really losing the battle?

It is first important to understand that cancer is not one disease, but a family of diseases where each member had its own idiosyncrasies despite their familial similarities. Thus, each cancer type has its own pathogenesis and should require a specific standard of care (prior to getting into the issue of personalized medicine). So research efforts are diluted by focusing on one cancer type or a group of cancers. Yet, the multifariousness of cancer ailments is not the chief obstacle in combating the disease.

The Elusiveness of Cancer

Imagine an African nation protecting itself against espionage. If the culprits were, say, Swedish, they would be easily detected. Even if the spies originated from a neighboring and ethnically-similar country, the counter-intelligence agency would still be able to close in on them, as they would lack an identification card indicating they are citizens of that country. But were a native to go rogue and provide intelligence to another country, that citizen would be much harder to identify. Indeed many intelligence agencies would prefer employing a native to gather intelligence, rather than instilling a foreigner into the target country.

Cancerous cells are natives that went rogue. The immune system can detect and fight foreign cells. They do this by checking the ID of each cell, coded in a certain class of proteins which are situated on each cell’s membrane. But as cancerous cells are indigenous body cells waving the patriotic flag, the immune system does not recognize these cells as a foreign threat. The cleverness of cancerous cells is even more striking. They alter specific gene expression and their own microenvironment to mask themselves from sentinels of the immune system. It is as if they don an immune invisibility cloak. For example, cancer cells present on their surface a certain protein which bind to receptor on immune cells, signaling the immune cell to commit suicide. Thus, the cancers cells keep their immediate vicinity (microenvironment) clean from any immune cells.

To combat these conniving cells, the traditional three pillars of treatment are surgery, radiation and chemotherapy. Surgery can be highly invasive. Furthermore, it is limited only to solid tumors that can be accessed and removed, and finally it is not effective against metastatic tumors (cells that detach from the mother-ship and migrate to inhabit other organs). Radiation and chemotherapy are generally systemic, meaning they affect any dividing cell in the body, which leads to an uncomfortable and often debilitating treatment period.

Immunotherapy: the fourth pillar of cancer treatment

Oncological treatment is undergoing a slow but steady revolution, and the old, less effective and systemic treatments are being superseded by sophisticated and targeted therapies in a field called immunotherapy. Immunotherapy uses elements of the immune system, most notably antibodies, for therapeutic purposes. The antibodies are designed to identify cancerous cells and reveal them to the immune system. Such treatments have already been approved and are in clinical use against certain kinds of cancers. Keytruda (Merck) and Opdivo (Bristol Myers-Squibb) are such antibodies. They are directed to those proteins that trigger cell death in immune cells. In effect, the immune cells can approach, survey and ultimately battle the cancer cells. Both these biologics (drugs that are of a biological nature as opposed to a pharmaceutical drug, which is a chemical compound) are approved for melanoma treatment, and have been approved for treating relevant lung cancers. It is a vote of confidence in this technology to have both these biologics  included in Israel’s Drug Panel list for treating lung cancer.

In the following article I will write about a new line of immunotherapeutic treatment in development that seems so akin to science fiction, that traditional treatments appear primitive in comparison.

[1] See report in Ha’aretz, Ynet and Maariv

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