What happens if chemotherapy does not work?

Doctors use chemotherapy either as a first-line therapy or in combination with other treatments, such as surgery. If chemotherapy does not work, a person may need to consider other treatment options.

Signs that cancer is not responding to chemotherapy include:

tumor not shrinking

tumor growing

cancer spreading from its original site to other areas of the body, which is called metastasis

cancer symptoms returning

additional symptoms appearing

Depending on the type and stage of cancer, second-line or third-line treatment options may be available.

In this article, we explain some of the alternative cancer treatment options if chemotherapy is not working. Below is a list of scientifically proven cancer treatments that can serve as either complementary or primary treatments.

Radiation therapy

Radiation therapy uses radiation to kill cancer cells and reduce the size of tumors.

Radiation therapy can serve as a primary treatment, but it also works well with other treatments, such as surgery.

Radiation therapy damages the DNA in cancer cells to the extent that they can no longer repair themselves.

These damaged cancer cells will stop dividing and eventually die, at which point the body will break them down and remove them.

There are two different types of radiation therapy, which are called external beam radiation therapy and internal beam radiation therapy.

External beam radiation therapy is a local treatment, which means that it targets a specific part of the body.

This form of radiation therapy uses a large machine that sends radiation from several directions to the required area.

Internal beam radiation therapy uses a radiation source that doctors implant inside the body near the tumor. It affects a smaller area of the body than external radiation therapy.

The implants that doctors use in this therapy can be either permanent or temporary. Temporary implant removal usually occurs after a few minutes or days. People with temporary implants are radioactive until the removal of the implant, while permanent implants gradually stop giving off radiation over time.

Advantages of radiation therapy

Radiation therapy has several advantages, including:

causes only moderate pain

minimal or no hair loss

effectively kills large numbers of cancer cells within a tumor

relatively safe for the individual as the radiation specifically targets the tumor

minimal damage to organs near the tumor

However, it is important to note that the intensity of pain will differ from person to person, and the damage to organs will vary depending on their location in relation to the tumor.

Disadvantages of radiation therapy

There are also several disadvantages of radiation therapy, such as:

people who receive internal beam radiation therapy will be radioactive for a short period

potential damage to vital organs if they are particularly close to the tumor

may not kill all cancer cells if the tumor is very large

inconvenient and time-consuming as people require treatment on 5 days of the week, and it can last for up to 2 months

expensive, although the exact cost depends on the type and amount of treatment

skin redness or soreness around the site of radiation

site-specific side effects — for example, treating cancer in the esophagus or gastrointestinal tract can cause nausea or vomiting

Immunotherapy

Some types of cancer do not respond well to radiation or chemotherapy, so a person may need to try immunotherapy.

Immunotherapy aims to help the immune system fight cancer in the same way that it fights infections and foreign pathogens.

Immunotherapies either stimulate the immune system in a general way or train it to attack cancer cells directly.

The main methods of delivering immunotherapy include:

Monoclonal antibodies: With this method, a person receives synthetic antibodies that bind to specific proteins on cancer cells. This binding marks the cancer cell to help the immune system locate and destroy it.

Checkpoint inhibitors: These are medications that stimulate T cells, which then identify and attack cancer cells more efficiently.

Cancer vaccines: Vaccines stimulate the immune system to fight cancer. Some vaccines, such as the human papillomavirus (HPV) vaccine, can have protective effects. Specific types of HPV are known to cause certain cancers.

Adoptive cell transfer: This involves removing T cells from a tumor and modifying them in a laboratory. After about 2 to 8 weeks, doctors return the T cells to the body. The aim is to boost the ability of the T cells to detect and destroy cancer cells.

Advantages of immunotherapy

Immunotherapy may work when other treatments do not. Its other potential advantages include:

effective against many types of cancer

can improve the success of other treatments

causes fewer side effects than treatments that target all the cells in the body, such as chemotherapy

after learning to target cancer cells, the immune system remembers this response if cancer reappears

Disadvantages of immunotherapy

The disadvantages of this form of treatment include:

risk of overstimulating the immune system and causing it to attack healthy organs, which can lead to severe complications in the lungs, intestines, kidneys, or other organs

side effects, such as fatigue, cough, nausea, loss of appetite, skin rash, and flu-like symptoms.

Source: Medical News Today

Hormone therapy

Hormone therapy can treat some types of cancer, including prostate cancer and breast cancer, by taking advantage of the disease's dependence on hormones to grow.

Hormone therapy works by either stopping the body from producing hormones or interfering with how hormones affect the body.

Hormone therapy to treat breast cancer, or anti-estrogen therapy, focuses on lowering estrogenlevels.

The treatment may involve surgical procedures, such as removal of the ovaries, or medications that interrupt signals from the pituitary gland, a gland that stimulates estrogen production.

Hormone therapy to treat prostate cancer, or androgen-suppression therapy, lowers testosteroneand dihydrotestosterone (DHT) production. Treatments include surgical procedures to remove one or both testicles and medications that prevent the production of testosterone and DHT.

Advantages of hormone therapy

Advantages of hormone therapy include:

effective treatment for preventing the spread of cancer to other parts of the body

can help reduce the risk of cancer returning after surgery

Disadvantages of hormone therapy

There are some disadvantages to this type of treatment, such as:

only works on cancers that require hormones to grow

side effects for females include headaches, hot flashes, weight gain, and vaginal dryness

side effects for males include fatigue, hot flashes, breast sensitivity or enlargement, nausea, impotence, and lower sexual desire

Targeted therapy

Targeted therapy uses medication that specifically targets cancer cells, destroying them from the inside.

Unlike chemotherapy, these medications do not affect healthy cells because they identify particular genetic abnormalities in cancer cells. Targeted therapy works best in combination with other treatments.

There are many types of targeted therapy, and they employ different methods to fight cancer.

Targeted therapies may fight cancer by:

blocking or turning off chemical signals that stimulate cancer cell growth

changing proteins inside cancer cells, causing cell death

preventing cancer cells from stimulating the growth of new blood vessels

triggering an immune response to destroy cancer cells

delivering toxic substances to cancer cells to kill them without affecting other cells

How destroying a tumor promoter could lead to new cancer treatments

Scientists have cracked a cell mechanism that drives tumor formation in most types of cancer. This finding could lead to much-needed new therapies for cancer, including the hard-to-treat triple-negative breast cancer.

The discovery concerns the molecular activity of the tumor suppressor protein p53. This protein sits inside the nucleus of the cell and protects the cell's DNA from stress. It has acquired the nickname "guardian of the genome" for this reason.

However, mutated forms of p53, which are common in cancer, behave differently than regular p53. Instead of protecting the cell, they can take on oncogenic, or tumor-promoting, properties and become active drivers of cancer.

Previous studies had already shown that p53 mutations are more stable than their nonmutant counterparts and can accumulate until they eclipse them in the nucleus. However, the mechanism behind the stability of p53 mutations remained unclear.

Now, researchers from the School of Medicine and Public Health at the University of Wisconsin-Madison have unpicked the stabilizing mechanism, and they suggest that it offers a promising target for new cancer treatments. Their findings feature in the journal Nature Cell Biology.

The stabilizing process involves two molecules: the enzyme PIPK1-alpha and its "lipid messenger" PIP2. Between them, they appear to regulate the function of p53.

"Although p53 is one of the most commonly mutated genes in cancer," says co-lead researcher and study author Vincent L. Cryns, who is a professor of medicine, "we still do not have any drugs that specifically target p53."

'Guardian of the genome'

The p53 protein protects the genome in several ways. Inside the nucleus, it binds to DNA. When ultraviolet light, radiation, chemicals, or other agents inflict damage on DNA, p53 decides whetherto repair the damage or instruct the cell to self-destruct.

If the decision is to repair the DNA, p53 triggers other genes to start this process. If the DNA is beyond repair, p53 stops the cell from dividing and sends a signal to begin apoptosis, which is a type of programmed cell death.

In this way, nonmutant p53 prevents cells with damaged DNA from dividing and potentially growing into cancerous tumors.

However, many mutant forms of p53 involve a change to a single building block, or amino acid, in the protein molecule, which prevents it from stopping the replication of cells with damaged DNA.

Using a range of cell cultures, the team behind the new study discovered that the PIPK1-alpha enzyme links up with p53 to make PIP2 when cells become stressed due to DNA damage or another cause.

PIP2 also binds strongly to p53 and causes the protein to associate with "small heat shock proteins." It is this association with heat shock proteins that stabilizes mutant p53 and allows it to promote cancer.

"Small heat shock proteins are really good at stabilizing proteins," Prof. Cryns explains.

"In our case, their binding to mutant p53 likely facilitates its cancer-promoting actions, something we are actively exploring," he adds.

Targeting p53 to fight cancer

The scientists were surprised to find PIPK1-alpha and PIP2 in the nucleus of cells, as these two molecules tend to occur only in cell walls.

They also found that disrupting the PIP2 pathway prevented the accumulation of mutant p53, effectively stopping it from promoting tumor development.

The team suggests that getting rid of mutant p53 could be a powerful way to fight cancers in which it is the key driver.

This could be a promising route for discovering drugs to treat triple negative breast cancer, an aggressive type which, by its nature, has few other drivers for drugs to target.

The researchers are already trawling for compounds that block PIPK1-alpha and could become candidate drugs for the treatment of tumors with mutant p53.

"Our discovery of this new molecular complex points to several different ways to target p53 for destruction, including blocking [PIPK1-alpha] or other molecules that bind to p53."

Prof. Vincent L. Cryns

Source: Medical News Today

How does tumor acidity help cancer spread?

By probing what happens to cells in acid regions of tumors, scientists have uncovered new information about cancer's invasiveness and spread. The discovery could lead to better treatments for aggressive tumors.

Researchers at the Massachusetts Institute of Technology (MIT) in Cambridge found that acidic, or low-pH, tumor regions alter gene expression in cancer cells in ways that make them more aggressive.

In a paper that appears in the journal Cancer Research, they describe how, by reducing tumor acidity, they were able to reverse the process in mice.

"Tumor acidosis," says first study author Nazanin Rohani Ph.D., who was a postdoctoral researcher in the Koch Institute for Integrative Cancer Research at MIT when she completed the work, "gives rise to the expression of molecules involved in cell invasion and migration.

"This reprogramming, which is an intracellular response to a drop in extracellular pH, gives the cancer cells the ability to survive under low-pH conditions and proliferate."

Metastasis and tumor environment

Metastasis is the complex process through which cancer cells become mobile, detach themselves from primary tumors, invade nearby tissue, migrate, and then set up secondary tumors in other parts of the body.

Around 9 in 10 of all deaths to cancer "are related to metastasis." Without metastasis, cancer would be a much more manageable and less severe disease.

There was a time when scientists believed that the potential for tumors to metastasize depended only on alterations to cancerous cells.

Since then, however, researchers have learned that the "malignant progression of cancer" also depends on cancerous cells participating in an "intricate network of interactions" with other parts of the tissue that surrounds them, or the tumor microenvironment.

There is now a good understanding among scientists that tumors are not simply collections of multiplying cancerous cells, but "living entities," comprising many different types of cell. In fact, the complexity of tumor tissue "may even exceed" the complexity of healthy tissues.

The study that Dr. Rohani and her colleagues undertook adds to the growing body of knowledge about tumor microenvironments and their contribution to metastasis.

Mapping tumor acidity

Previous research had already established that acidity in the tumor microenvironment had a powerful effect on cancer invasiveness. However, what was not clear was how acidity varied in a tumor, and how it might alter genes to make tumor cells more invasive.

Before the recent study, the prevailing view was that high acidity in tumors occurred mainly in oxygen-starved areas with a poor blood supply.

For their investigation, the MIT researchers used a "pH-probe" to map acidity in breast cancertumors in mice.

When the pH-probe detects a cell in an acidic environment, it inserts a small protein molecule into the cell's membrane. In this way, the researchers can tag and identify cells in acidic regions of the tumors.

To its surprise, the team found that acid regions were not only present in hypoxic, or oxygen-starved, pockets inside tumors. The surfaces of tumors — where they connect to the stroma, or "structural tissue" that surrounds them — also contained acidic regions.

This discovery suggested that oxygen-starvation was not the main reason for acidity in tumors. On closer investigation, the scientists found a different cause of microenvironment acidity at the tumor surface.

Reducing tumor acidity

It appeared that the metabolism of many of the cells on the surface of the breast tumors had changed to aerobic glycolysis. This type of metabolism produces lactic acid, which made the tumor microenvironment more acidic.

In these acidic tumor surface regions, the cells had altered their genes to switch on processes that favor invasion and metastasis.

The activated genes included one that is involved in embryo development and produces a protein that aids cell migration via the bloodstream. Another was one that makes tumor cells more able to penetrate their surrounding tissue.

In another set of experiments, the team found that reducing the acidity of the tumor microenvironment returned the gene expressions almost back to normal.

The researchers reduced tumor acidity in the mice by adding sodium bicarbonate to their drinking water. Other studies have also found that this reduces metastasis in mice.

Senior study author Frank B. Gertler, who is a professor of biology at MIT, says that humans do not tolerate sodium bicarbonate, and so it would not be a suitable potential treatment for them.

"Other methods that would more focally target acidification could be of great value."

Source: Medical News Today

Surgery with ultrasound treats high blood pressure in trial

A minimally invasive surgical procedure that targets nerves leading to the kidneys could one day offer a safe way for some people to reduce their blood pressure medications.

Investigators have announced the 6-month results of an international clinical trial on the safety and effectiveness of renal denervation by ultrasound as a treatment for mild to moderate high blood pressure.

The findings featured recently at the American College of Cardiology Conference in New Orleans and in a study paper in the journal Circulation.

Surgeons carry out the procedure, which takes about 1 hour, under local anesthetic. It decreases activity in nerves that link the brain to the kidneys and carry signals that regulate blood pressure.

The 2-month results from the randomized, controlled trial had already shown that the procedure resulted in a more significant reduction in blood pressure, compared with a "sham operation."

None of the people in the trial took their blood pressure drugs during the first 2 months. They then resumed blood pressure medication in a managed way, as necessary.

Now, the more recent results reveal that the participants who underwent the ultrasound surgery maintained their reduced blood pressure for 6 months.

Compared with those who had the sham operation, fewer participants who had the surgery needed to resume blood pressure medication, and those who did required fewer drugs at lower doses.

"These results," says lead trial investigator in the United Kingdom Melvin D. Lobo, a professor at Queen Mary University in London and also of Barts Health NHS Trust, both in the U.K., "point towards an exciting future for this new technology."

Hypertension and kidney nerves

High blood pressure, or hypertension, is a growing global health issue. According to a report in The Lancet, between 1975 and 2015, the number of adults living with high blood pressure rose from 594 million to 1.13 billion.

Having high blood pressure increases the risk of heart disease, heart failure, and other conditions.

Some people can keep their blood pressure under control by watching their weight, doing plenty of exercise, and maintaining a healthful diet. Others may need to supplement these measures with medication.

However, some people struggle to control high blood pressure even with lifestyle changes and medication.

The kidneys have a rich system of nerves for sending and receiving messages.

Scientists have discovered that overactivity in this system can raise blood pressure through its interaction with the body's sympathetic nervous system.

Renal denervation by ultrasound is a treatment that aims to relieve high blood pressure by disrupting the nerves leading to the kidneys.

The procedure involves inserting a device through a catheter in the groin to reach up into the artery of a kidney. The device emits ultrasound waves that then heat up and damage some of the nerve fibers that surround the artery.

Source: Medical News Today