Normalizing Tumor Microenvironment Enables Novel Cancer Therapies

Key Quotes

"a tumor is more than a bag of cancer cells it's like an organ which has gone awry it's an organ which has its own rules and if we can figure out those rules we can improve not only detection but treatment of cancer and improve lives of patients"

Dr. Jain argues that a tumor should not be viewed simply as a collection of abnormal cells but as a complex organ with its own governing principles. He explains that understanding these underlying rules is key to advancing both the detection and treatment of cancer, ultimately benefiting patients.

"when i entered the field and even today most people focus on the cancer cells but i decided to focus is what you call the soil and uh i found out the soil it not only helps tumor grow that's understandable but also confers resistance to every form of therapy radiation therapy chemotherapy immunotherapy and all the future therapies which will be coming along"

Dr. Jain highlights his decision to shift research focus from the cancer cells themselves (the "seed") to their surrounding environment (the "soil"). He discovered that this tumor microenvironment not only supports tumor growth but also plays a critical role in conferring resistance to various cancer therapies.

"so i said to myself hold hold a second how can you deliver a drug if you cut off the blood supply what why would it make work better so in the meantime while i was doing experiments in mice i was seeing that when he give this drug you actually improve the blood supply so it does the exact opposite the opposite you got it"

Dr. Jain recounts his realization that anti-angiogenic drugs, intended to starve tumors by cutting off blood supply, paradoxically improved drug delivery in his experiments. He explains that these drugs actually enhanced blood supply, leading him to question the prevailing dogma and pursue a new therapeutic direction.

"normalizing vessels using anti drugs that were developed to kill them how did that go i was not they did not go well i will not dwell on it because i could give you a long history about my grant rejections paper rejections on and on but anyway what was the worst review just give one example well when somebody wrote to me what's dr jain smoking"

Dr. Jain describes the initial resistance and skepticism he faced when proposing the idea of using anti-angiogenic drugs to normalize tumor blood vessels, rather than destroy them. He shares an anecdote about a harsh review that questioned his sanity, illustrating the challenging reception his unconventional ideas received.

"human tumors apply pressures higher than 120 millimeters of mercury you know what i mean arterial blood pressures are about 100 so a tumor can compress apply pressure more than your heart can pump okay so it's a it's high pressure it's a high pressure zone it collapses which kind of explains why your your blood vessels are crimped you got it it collapses"

Dr. Jain explains that tumors generate significant internal pressure, exceeding normal arterial blood pressure, which leads to the collapse of blood vessels within the tumor. He details how this high-pressure environment impedes blood flow and drug delivery, presenting a critical challenge in cancer treatment.

"and you discover this cheap generic blood pressure medicine losartan that seems to reinflate the blood vessels is that sound right yeah it removes them yeah it it what does it do does it get rid of the matrix yeah what it does it reduces it same thing normalize it"

Dr. Jain confirms that the blood pressure medication losartan was found to reduce the matrix within tumors, thereby normalizing the tumor microenvironment and alleviating the pressure that collapses blood vessels. He emphasizes that this generic and inexpensive drug effectively "reinflates" the vessels by reducing the matrix, rather than removing it.