Revamped cancer drug starves tumors in mice | Science | AAAS

Good morning all,

As I noted in lecture on Wednesday, we remain caught-up with our lecture schedule and do not have chapter assigned for today.  So, we will not meet in person for class today; instead I will offer this reading which I would like to you to consider.

In our last lecture, we identified the "cell cycle" as a way to describe the normal lifespan of a cell, from its formation, through its functional life, and then its eventual end.  All of our body cells are formed from mitotic cell division to begin their life, and, at the end of their functional lives, many of our cells undergo division themselves, essentially being reborn as two new daughter cells.

We also identified important "checkpoints" in the cell cycle, to prevent cells from speeding through the cell cycle too rapidly.  Many of our cells have functional lives of months to years, and without these checkpoints, they would otherwise just divide rapidly into new cells.  As we noted, failure to stop at these cell cycle checkpoints can lead to tumors caused by uncontrolled growth; some tumors can become cancers, invading otherwise normal tissues and causing them to become cancerous as well.

As you know, cancer is one of the primary causes of human mortality.  We experience a variety of cancers: some are slow to progress, others very rapid; some are essentially benign while others are very deadly; some are highly invasive and others less so.  The diversity if cancers we experience and the diversity of tissues that they strike represents one the of the primary difficulties in treating cancer: there is no single cure, for cancer is very diverse in its many forms.

That's not to say that there aren't standardized treatments.  Most hospitals have oncology boards that carefully document each occurrence of cancer, and they typically made treatment decisions based upon consultation among a team of physicians, including oncologists, radiologists, surgeons, and others.  Much of their decision-making is based upon care standards that have been developed by national and international cancer agencies, such as our own American Cancer Society, which suggests treatment guidelines for the different forms of cancer.  Still, we know all too well that curing cancer is difficult, and sometime impossible.  The best one can hope for is to eliminate the cancerous tissue to the point at which is cannot be detected, but that is no promise that every cancerous cell has been removed, nor that it cannot re-appear.

Because of the burden cancer poses to society, there are many federally-funded research groups investigating potential treatments.  These include

• genetic methods - to identify and correct cancerous genes, those causing failure of cell cycle checkpoints
• immunological approaches - training our immune cells to hone-in on cancerous cells
• pharmacological methods - using drugs to kill cells which are undergoing cell division
• metabolic methods - starving tumors and cancers of their blood supply or metabolites

Of course, many of the latest treatments combine multiple approaches, such as using immune cells to target delivery of cytotoxic drugs directly to cancer cells.

In the news this week is report of a promising new approach to treating some kinds of cancer, based upon a metabolic starving of cancer cells.  Cells that are rapidly dividing (such as those within a tumor or a cancer) are metabolically very demanding, needing large amounts of fuel.  Scientists have developed methods to prevent cells from using glutamine (a glucose-like fuel source), to successfully prevent cancer growth.  But, earlier formations of this treatment caused widespread side effects, because the cancer cells were not the only ones being starved of fuel. 

In this latest test, the scientists successfully "handcuffed" an inactive form of their drug to allow its focal delivery to cancer cells, where it was "unhandcuffed" into an active form by cancer cell enzymes.  There it successfully prevented cancer growth.  Even better, this new treatment actually improved immune T-cell function, providing an immunological boost to cancer elimination as well.

These initial studies, done in mice, were very promising.  While the road from animal studies to human uses is often long and unsure, this could mark the beginnings of a new generation of cancer treatments that are improved in their focused targeting as well as in their effectiveness at cancer elimination.

https://www.sciencemag.org/news/2019/11/revamped-cancer-drug-starves-tumors-mice

We'll talk more about cancer in our upcoming lectures, and I hope that this article will put some of the lecture material into practical context.  Cancer touches many families, and does not discriminate by race, class, knowledge, or upbringing.  May your generation be the one that finally reduces the impact that it has on our individual and our public health.

Have a great weekend - see you on Monday.

Sincerely,
Dr. Nealen