Will Cancer Ever Be Cured?

bald woman with cancer wondering if the disease will ever be cured

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Many people wonder if cancer will ever be cured, or how close we are to a cure. In turn, responses to this question span the spectrum, with some emphasizing that cancer includes a wide range of complex diseases that will never be cured, and others suggesting it will be eliminated in a particular time span. Other people comment that our greatest hope is to be able to control cancer as a chronic disease. Let's look at some of the obstacles that are preventing the cure of more cancers, issues that must be overcome, and the ways in which research is advancing to bring us closer.

Cancer Isn't One Disease, Though Commonalities Exist

A very important first point when talking about a "cancer cure" is that cancer isn't a single disease. There are hundreds of different types of cancer, and, in fact, no two cancers are the same. Two cancers of the same tissue type, subtype, and stage may have significant molecular differences; differences that can play a considerable role in available treatment options and outcome.

This isn't surprising as cancer therapy can be seen as analogous to the treatment of infectious disease. We don't have a single "cure" for strep throat, Lyme disease, and tuberculosis. And that doesn't go beyond bacterial infections to include viruses, fungi, and parasites. Even when effective options are available for specific infections, every person responds differently to treatments available, and pharmacogenomics (knowing how a person's genetic make-up influences how they respond to drugs) is only in its infancy. Similarly, just as some microbes find ways to "hide" in the body so they can return at a later date, cancer cells often find ways to escape both cancer treatments and our immune system.

Unlike microorganisms, cancer cells begin as normal cells in our bodies, making them much more difficult to treat. Treatments that eliminate cancer cells may eliminate similar "normal cells" in body, and this is the basis of many of the annoying side effects of chemotherapy.

While cancer isn't one disease, or even hundreds of diseases, there are some commonalities that are now being addressed with hope of treating different cancer types.

Commonalities

The fact that cancer isn't one disease is evident in the conventional treatment approaches. Treatments for lung cancer differ for those of breast cancer, and so on.

Yet recent advances are exploiting the similarities between different cancers in order to treat them. This isn't surprising as roughly 90 percent of cancer-related deaths are due to metastases, and the ways in which errant cells spread to regions where they don't belong has some commonalities among tumor types. For example, cancer cells often lose proteins referred to as "adhesion molecules" that cause them to stick to nearby cells. This makes the cells more likely to "break loose" and travel via the blood or lymph fluid to other parts of the body.

In addition, there are several changes that take place to transform a normal cell to a cancer cell, and the pathways associated with these changes often overlap.

There are now two drugs that have been approved that take advantages of these commonalities and appear to work across cancer types. The checkpoint inhibitor (a type of immunotherapy drug) Opdivo (nivolumab), a drug that can be thought of as taking the mask off of cancer cells so they are recognized by the immune system, is now approved for some people with metastatic non-small cell and small cell lung cancer, melanoma, liver cancer, Hodgkin lymphoma, head and neck cancer, and kidney cancer.

A different drug considered a form of targeted therapy is approved for different cancer types that test positive for a gene alteration referred to as neutrophic receptor kinase (NTRK) gene fusion. The drug Vitrakvi (larotrectinib) may used for people with tumors positive for the gene fusion ranging from salivary gland tumors, sarcomas, thyroid cancer, colon cancer, lung cancer, and more.

Obstacles in Curing Cancer

Before discussing a number of obstacles that are preventing the cure and often even control of cancer, it's important to note that there are currently some cancers that can be cured.

Cancers That Are Currently Curable

Stage 0 cancers, such as ductal carcinoma in situ (DCIS) should in theory be 100 percent curable as they are not considered invasive (they haven't spread beyond something called the basement membrane). That said, even many small stage I tumors have the potential to recur after treatment, even if small, and aren't considered curable.

When talking about whether cancers are curable, many people look at 5-year survival rates. Looked at this way, cancers considered more curable include those such as breast cancer, melanoma, thyroid cancer, Hodgkin lymphoma, and others.

But "treatable" is different than "curable." For example, breast cancers that are estrogen receptor positive (stage I to stage III) are more likely to recur five to 10 years after diagnosis than in the first five years, and sometimes recur even decades later.

While these cancers may be considered more "treatable" as there are more options, they are, in a sense, less "curable" than those that are not hormone receptor positive. Instead of "cured," oncologists may use terms such as "no evidence of disease" (NED) or complete remission. In some cases, the term "durable response" may be used when it appears long term control of a metastatic cancer is possible.

With some cancers, such as childhood leukemia and Hodgkin lymphoma, the chance of the cancer returning in adulthood after successful treatment is very low and many oncologists will refer to someone as "cured," for example, if they had acute lymphoblastic leukemia as a child. So what are the issues that are holding us back from curing other cancers?

Cancers Change

There's a tendency to think of cancer as an unchanging clone of abnormal cells, but that's not the case at all. Cancer cells are continually changing and acquiring new mutations. These new mutations may give rise to new characteristics of the cancer, such as the ability to spread more freely. Non-genetic "epigenetic" changes also occur.

Resistance

Changes in cancer cells lie behind much of the resistance to treatment that's seen with cancer. While a tumor may initially respond to a treatment such as chemotherapy or a targeted therapy, cancers often find ways to bypass these treatments and continue to grow.

At the current time, many available targeted therapies are able to control the growth of a tumor for a time before resistance develops. In some cases next generation drugs are available that allow people to stay ahead of this resistance, but tumors often again change. A significant amount of research is currently focused on looking upstream and downstream in the growth pathway of a particular tumor to identify other targetable places to halt growth.

In some cases, these changes can result not only in resistance, but the transformation of a tumor into a competely different subtype of cancer. For example, some EGFR positive non-small cell lung cancers may transform to small cell lung cancer, a much more difficult type of cancer to treat.

Cancers Enlist Help From Normal Cells/Tissue Microenvironment

Not only do cancer cells have an ability to hide and adapt, they often enlist help from normal cells in their surroundings. These nearby cells such as fibroblasts, macrophages, and much more can be coerced to secrete compounds that help a tumor grow. (This recruitment of normal cells to do the dirty deeds of a cancer is something that can't be studied in a dish in the lab, and adds to the challenges of understanding and treating cancer).

Some of the ways in which cancers recruit normal cells include coercing normal cells to secrete substances that cause blood vessel growth (angiogenesis) to feed the tumor or suppress the immune system.

Heterogenicity of Tumors

Another characteristic of cancers is heterogeneity. Not only do cancer cells continually change how they behave and adapt, these changes can be different in different parts of a tumor. Due to these changes, one part of a tumor may be sensitive to a treatment while another part of the tumor (or a metastasis) may be resistant.

Balance: Efficacy vs. Toxicity

Another reason cancers can be so challenging to treat is the balance between effectiveness of therapies and side effects (toxicity). Adding immunotherapy drugs to the arsenal of cancer treatments has resulted in dramatic responses for some people, but also illustrates the precise balance in our bodies and how treatments can alter that.

With the immune system there is a delicate balance between being overly active (and when so, attacking the bodies own tissues resulting in autoimmune disease) and being underactive, such that tumors grow unchecked. For this reason, the most common side effects of commonly used immunotherapy drugs include almost anything that ends in "itis" referring to inflammation. (On the flip side of this, immune modulating drugs such as some used for rheumatoid arthritis can increase the risk of developing cancer.)

Study Limitations

Most drugs for cancer are first studied on cancer cells grown in a dish in the lab and in animal studies. Unfortunately, what works in a dish in the lab (in vitro) does not often translate to effectiveness in the human body (in vivo). For example, according to a 2018 review, it's thought that roughly 90 percent of drugs that appear to be effective in lab studies fail to work when studied on humans in clinical trials.

Animal studies also have significant limitations, and humans differ from mice in a number of ways. The effectiveness of a drug in mice does not guarantee effectiveness in humans. Likewise, side effects found in mice may differ greatly from those seen in humans. Cost is also a huge issue.

Newer Treatments and Advances

The past decade has seen several advances in diagnosis and treatment, and mentioning a few of these is helpful when it feels like progress is far too slow.

Targeted Therapies (Control, Not Cure)

Targeted therapies, while not a cure (though there are a few outliers that appear cured), can sometimes control a cancer for a significant period of time. The story of Gleevec (imatinib) is a classic example of how discovering a genetic alteration in cancer has allowed researchers to design a treatment than can often control the cancer long term.

With most cancers, resistance develops, though second and third generation drugs for some mutations (such as EGFR mutations in lung cancer) are allowing some people—for a time at least—to control their cancer as a chronic disease much like high blood pressure or diabetes.

The ability to identify genomic alterations (gene mutations, rearrangements, etc.) is also expanding rapidly. While single tests only a few years ago might detect a specific alteration, tests such as next generation sequencing now allow physicians to examine many potential alterations that may be treatable.

Immunotherapy

We've known for some time that on rare occasions a person may experience the spontaneous remission of cancer, even an advanced cancer. It's now thought that in some cases, the immune system may fight off a cancer. Our immune systems know how to fight cancer, and have cells that are powerful cancer fighters such as T cells. Unfortunately, cancer cells have discovered the ability to suppress that immune response so that cancer cells can grow unchecked.

The type of immunotherapy known as checkpoint inhibitors work by essentially "unmasking" cancer cells so they can be recognized. While these drugs can sometimes result in dramatic responses (what's termed a durable response) in advanced cancers such as metastatic lung cancer or melanoma, they only work on a minority of people. Future research lies in looking for ways in which more people will respond.

An interesting finding has been that the effectiveness of checkpoint inhibitors is related to the diversity of gut bacteria (the gut microbiome). Future research into ways to increase diversity of the gut microbiome (probiotics didn't do it) is needed to see if it's possible for these drugs to be effective for more people.

It's also been found that using radiation therapy in combination with immunotherapy can sometimes improve control. Via something called the "abscopal effect," the death of cells caused by radiation therapy may (via the tumor microenvironment) activate immune cells that can subsequently attack tumor cells far away from the site where radiation was delivered.

Treatment of Oligometastases

As noted earlier, metastases are responsible for most cancer deaths, and while in the past the spread of cancer to other regions of the body was treated with general therapies, specific treatment of solitary or only a few metastases has now been found to improve survival for some people.

Sometimes a metastatic cancer may be reasonably controlled on a treatment, but a new metastasis starts or continues to grow (a "rogue" tumor). Treatment of these areas with methods such as stereotactic body radiotherapy (SBRT) with a curative intent may sometimes eradicate these rogue tumors, allowing a cancer to again be controlled.

Future Directions

Three are many approaches both already available and in the works that promise to improve our understanding, and hopefully treatments for cancer.

Studying Outliers

For a very long time it's been known that some people respond particularly well to certain treatments, though this has often been considered a fluke. Rather than dismissing these people, however, researchers are now interested in trying to find out why a rare person might respond to a treatment.

An example from the recent past to illustrate this is that of the EGFR inhibitor Iressa (gefitinib) that was initially approved for non-small cell lung cancer in 2003. Given that the majority of people did not respond to the drug, access was restricted in 2005 to only those people who had responded.

Since that time the discovery of the role of EGFR mutations in some lung cancers (roughly 15 percent of non-small cell lung cancers) resulted in the drug being approved in 2015, this time for people with EGFR exon 19 deletions and exon 21 (L858R) substitution mutations. In contrast to a very low rate of effectiveness originally, when given in the right setting the drug now works for the majority of people treated.

Understanding Recurrence

It's not certain exactly how cancer cells can hide, sometimes for decades, though there are theories such as the stem cell theory of cancer. Research into how, where, and when cancer cells "hide" may help researchers design methods for perhaps preventing the cells from hiding, or finding where they are hidden in order to eliminate them.

Understanding Metastases

Research is also ongoing to better understand how and why cancers spread to other parts of the body. It's now better understood that the environment in some tissues provides more fertile soil on which errant cells can arrive and grow, and prevention of at least some metastases is now thought to be possible.

Bisphosphonates (osteoporosis medications) such as Zometa and Bonefos had been used to treat bone metastases, but have now been found to reduce the chance that bone metastases will occur in the first place by altering the microenvironment of bone. This led to the approval of bisphosphonates for early stage breast cancer in postmenopausal women with estrogen receptor positive tumors who are also taking an aromatase inhibitor.

Liquid Biopsies

The recent development of liquid biopsies promises to help researchers better understand the changes that take place in tumors that allow them to become resistant to available targeted therapies.

With some tumors, specific "resistance mutations" (mutations that allow the tumor to escape the effects of the targeted drug and continue to grow) are now also targetable. Finding these mutations, however, has been challenging, as it required a sample of the cancer, sometimes meaning an invasive biopsy.

Blood tests (referred to as a liquid biopsy) are now available for some tumors that can detect mutations in cell-free DNA, and in some cases, provide information similar to that of a tissue specimen.

While too costly at the current time to be done very frequently, sequential blood tests looking for changes even before resistance develops (often found when a tumor begins to grow on a test such as CT scan) may both improve treatment (by allowing people to change their treatment before clinical changes are seen), and advance the science behind tumor resistance and progression.

Genetics

In addition to identifying genetic alterations that may be exploited to treat cancer, the completion of the human genome project offers hope for early detection of cancers in people at risk and possibly even prevention.

Genome-wide association studies are studies that look at people with an without a disease and then look for changes (single nucleotide polymorphisms) in the entire genome that may be associated with the disease. Surprising findings have already been made. For example, a condition once considered environmental—age-related macular degeneration—is now considered largely genetic in origin.

For many cancers, screening tests for early detection are not appropriate as they would do more harm than good (via measures such as invasive tests done for false positive results). Being able to identify people who are truly at risk might allow physicians to screen those people in order to find cancers (such as pancreatic cancer) at a stage when they are much more treatable.

What About CRISPR?

Some people have asked whether CRISPR (clustered regularly Interspaced short palindromic repeat) will cure cancer. Gene editing (CRISPR-Cas9) is certainly advancing the science that could aid in treatments, but it's unlikely that gene editing alone could be a cure in the near future.

One reason is that cancer is usually related to a series of mutations and not a single mutation (such as with some hereditary syndromes being studied). In addition, every cell in a cancer would need to be edited.

More potential could be seen in the use of CRISPR to edit cells in the immune system to better fight cancer. CAR-T immunotherapy is currently approved as a treatment for some cancers, though in this case the immune cells are not genetically engineered using CRISPR. CAR T-cell therapy is a form of adoptive cell therapy in which a person's own T cells are genetically modified to fight their cancer. A 2017 study on mice found that using CRISPR resulted in T cells that were more effective at killing cancer.

There are still safety issues to overcome, but it's likely that this technique will play a role in treatment as therapy becomes more personalized.

A Word From Verywell

The hope of finding a cure, or at least a way to control more cancers, cannot be understated. At the current time, one in two men and one in three women are expected to develop cancer during their lifetime, and far too many people still succumb to the disease.

There have been many recent advances in the treatment of cancer. As with those advances, it's likely that if a "cure" is found it will not be a one-size-fits-all approach, but rather a diverse range of precision approaches based on the unique molecular characteristics of a particular tumor. To deny it is possible, however, would be to dismiss the many advances in recent years. Advances that few people could have conceived a few short decades ago (or even a few years or a few months ago).

A very positive recent advance in the treatment of cancer has nothing to do with survival rates. Issues such as quality of life and survivorship have moved off the back burner and into the limelight where they belong. It's important that whatever advances are made in the future, that research continues to help people live well (and not only longer) with cancer.

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