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Finding ways to limit cancer recurrence

DR. NICHOLAS DEMOSTHENES

Anesthesia can suppress the immune system and enable cancer growth, so by using regional anesthetics, effects on the immune system can be minimized.

Advances in medicine enable many people to beat cancer or, at the very least, slow it down. However, beating the disease once doesn’t necessarily mean the end of that journey for some cancer patients. Recurrence is a common part of experiencing cancer — some patients are disease-free then get a second diagnosis while others are in remission but then experience progression of the disease again.

But there are many modern treatments that seek to reduce the risk of recurrence and to give patients better chances of long-term survival when fighting cancer.

Doctors must grapple with a multitude of factors when treating any kind of patient. Individual medical histories, the range of possible procedures, and the unpredictable nature of the job itself make for many complicating situations. Because of this, clinicians can find it difficult to prioritize steps relating to cancer recurrence when fighting the disease in the first instance often seems more pressing.

Physicians working in the field of anesthesiology, for instance, face this issue frequently. While this may seem bleak, research into specific treatments across the medical field aimed at limiting cancer recurrence, such as Tyrosine Kinase Inhibitors, or TKIs, are gaining popularity and support from the medical community.

ANESTHESIOLOGY

While cancer recurrence may seem like it should be a high priority for clinicians, practice sometimes tells a different story. For example, the field of anesthesiology could play a significant role in the consideration of cancer recurrence.

If you’ve had surgery, you may be familiar with general anesthesia. The medically induced coma that results from this cocktail of drugs has been the standard of care for many years, but a new class of anesthetics could change this. These newer drugs, known as regional anesthetics, target specific portions of the body as opposed to the system-wide approach of general anesthesia. Anesthesia can suppress the immune system and enable cancer growth. In limiting the affected area of the body by using regional anesthetics, effects on the immune system can be minimized.

“The use of regional anesthesia has quickly burgeoned into an important adjunctive tool when designing an anesthetic plan,” according to University of Pennsylvania anesthesiology resident Dr. Nicholas Demosthenes.

Research is beginning to show that these new types of anesthetics could have an impact on cancer recurrence in the surgeries in which they are used. For example, one 2016 study showed that a regional anesthetic known as propofol limited the spread of cancer in experiments outside of a living organism.

One might think that studies such as this would have an impact on how anesthesiologists tailor their treatment plans, but practice has yet to catch up to the research, Demosthenes said.

“We tend to focus on and prioritize avoiding acute complications like cardiac arrest, stroke and hemodynamic instability over more sub-acute complications like immunosuppression,” he said.

While it may take some time before hospitals and anesthesiologists begin considering cancer recurrence the same as they do cardiac arrest, other budding research looks to advance efforts to stem cancer recurrence.

TKI DRUGS

Tyrosine kinase inhibitors (TKIs) are a class of cancer drugs that are generally used in cases where standard chemotherapy drugs don’t work well. They’re commonly used for lung cancer, since chemotherapy usually doesn’t stop lung cancer from progressing. In the short term, TKIs tend to be very effective at treating lung cancers, research shows.

In general, TKIs work by inhibiting processes within cancer cells that cause “uncontrolled mitosis,” or cellular reproduction. When a cell is preparing to undergo mitosis, it will phosphorylate, or add a phosphorus atom to various molecules within the cell to allow the cell to split in two. One of the main signals to phosphorylate these molecules is given by the epidermal growth factor receptor protein.

In cancer cells, this protein sends out the signal to split far more than in a normal cell, leading to a rapidly expanding cluster of cells. Most TKIs used to treat lung cancer target the epidermal growth factor receptor protein, known as EGFR. The TKI chemically binds to the protein in a way that makes the protein unable to signal the cell to begin mitosis.

However, lung cancers generally acquire resistance to TKIs within a few years, meaning that the cancer stops being affected by the drug. For EGFR-targeting TKIs, this resistance occurs because the EGFR protein mutates and the TKIs can no longer bind and inhibit the protein’s function. The most common mutant is EGFR-T790M. After the initially used TKI stops working, secondary TKI and chemotherapy treatments are much less effective. Because of this, research into TKIs that can stem cancer recurrence is ongoing. For example, researchers have developed TKIs that are able to bind to and inhibit the EGFR-T790M mutant.

The new TKIs under development will give doctors a new set of drugs that can be used to improve medical outcomes and extend patients’ lives.

Cancer remains one of modern medicine’s least treatable diseases, and one of the most pervasive in our society today. Unlike most other diseases, it also has the potential to return after remission, or even after a patient has been declared cancer free.

Researchers are constantly working on developing more effective methods to prevent recurrence, like regional anesthesia and TKI drugs that are not affected by common resistance-inducing mutations.

Through life-saving innovation and development, cancer recurrence can be better understood, treated, and hopefully prevented altogether.

 

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