Falling Through the Cracks: Combating Chemo-Resistant Cancer Cells

Since Nixon started the War on Cancer in the 1970s, the standard for cancer treatment has been chemotherapy, in which a cocktail of cytotoxic drugs are given at dosages the patient can tolerate without dying himself or herself. Unfortunately, some patients' cancers, especially those who have underwent years of chemotherapy treatments, eventually develop resistance to these drugs, forming "chemo-resistance" to render these drugs ineffective.

In order to prevent chemo-resistant cancer cells from wreaking havoc upon their hosts' bodies, researchers at the H. Lee Moffitt Cancer Center have developed a novel cancer treatment method termed "adaptive therapy." As opposed to chemotherapy's heavy drug dosage, Moffitt's adaptive therapy subjects cancer cells to short bursts of drug administration. Head developer of the treatment and leader of Moffitt's Cancer Biology & Evolution Program Dr. Robert Gatenby describes these short bursts as being more effective, as it serves to control a chemo-sensitive population of cells that prevents chemo-resistant cells from growing uncontrollably. Thus, researchers minimize the risk of growing exclusively chemo-resistant cells, whereas conventional chemotherapy's intense drugging kills off almost all chemo-sensitive cells to indirectly permit chemo-resistant cells to subsequently flourish.

In one study conducted by Gatenby's team, scientists administered varying doses of chemotherapy drug paclitaxel to mice with the common breast cancer. Mice were separated into three groups differing in treatment strategy: one receiving the conventional maximum dose (ST), one receiving the adaptive therapy dose in which paclitaxel is administered at a constant frequency but its dosage is decreased every time the cancer responded (AT-1), and one receiving the adaptive therapy dose in which paclitaxel is administered in identical doses but drug administration is skipped every time the cancer responds to a previous drugging (AT-2). Overall, researchers found the AT-1 treatment to be the most effective in both controlling and killing off the cancer cell population, mice in the group surviving substantially longer than their counterparts in the other groups.

Adaptive therapy, whilst not providing a cure for cancer, provides a practical solution to better combating the disease, as it relies purely on treatment strategies. It definitely represents a step in the right direction.

Click below to learn more about adaptive treatment and Gatenby's group's findings.


Starving Out Cancer

One development in cancer research involves the development of a process to essentially "starve out" cancer cells. Akin to sieging a city in wartime, this treatment has become popular with doctors for its relatively noninvasive procedures. However, its popularity was accompanied by concerns regarding patients' health, as this treatment would involve decreasing their overall nutrient intake, thus starving the patient as well. Specifically, this treatment has been found to result in damage to tumor-infiltrating lymphocytes (TILs), one of the immune system's primary mechanisms in combating cancer.

One researcher, Dr. Valter Longo of University of Southern California in Los Angeles, has sought to devise a diet that both destroys cancer cells and funnels nutrients solely to non-cancerous body cells. In 2012, Dr. Longo employed his starvation method in tandem with anticancer drug doxorubicin on mice, receiving generally positive results, as tumors shrank by 4/5 of their size as compared to 1/2 with only drug treatment. In attempting to replicate the experiment in clinical human trials, he realized the risk involved in intentionally starving people. Thus, in order to maximize the method's benefits whilst minimizing its problems, Dr. Longo formulated a new diet rich in vitamin D, zinc, and fatty acids, all of which are integral to TILs' performance. This diet also minimized protein and simple sugars, both of which are readily taken up by cancer cells.

Hopefully, this cutting-edge treatment will be refined in future years for popular use, offering a more natural method of killing cancer.


Tailored to you: Personalized Treatment

Cancer has become less of a disease of certain organ than a genetic mishap turned tragic. As a result, oncologists have begun tailoring patients' treatment options to better fit their diagnoses, a practice known as "personalized medicine." In this, analyses of patients' biopsies point toward the use of a variety of drugs not usually prescribed in normal analyses. For example, the best treatment for one patient's case of breast cancer may be one already used in general treatment of colorectal cancer.

An integral part of personalized cancer treatment is the liquid biopsy, which analyzes genetic material shed by a tumor (circulating tumor DNA or ctDNA). Being non-invasive, fast, and cost-efficient, liquid biopsies will allow a doctor to frequently analyze their patient's ctDNA so as to determine whether to change their treatment if their patient's ctDNA changes. If the ctDNA does, in fact, change, it will allow the doctor to develop a new method of treatment specifically designed to treat that type of cancer, thus combating the disease more efficiently overall.

While I cannot say liquid biopsies are the key to curing cancer, they are certainly a step in the right direction.

Turning Our Bodies Against Cancer: Immunotherapy

Recently, a novel cancer treatment method has made great strides in efficiency: immunotherapy. Basically, immunotherapy studies how our immune system naturally deals with and fights cancer.

In this treatment, T-cells are enabled to identify and kill cancer cells posing as normal cells. Typically, cancer cells are coated with receptors known as PD-1, PD standing for "Programmed Death." These receptors initiate cell apoptosis, or cell suicide, in T-cells. Usually utilized to restrain the immune system from attacking the body, like in autoimmune diseases, PD-1 receptors are abused by cancer cells to not only escape detection by the immune system, but also to make the body less able to fight off other infectious agents.

The treatment drug, known as nivolumab, acts as a PD-1 inhibitor, disabling PD-1 receptors and their effect on T-cells. This allows the immune system to fight off cancer much more effectively, as it can both identify and kill cancer cells once treated.

Unfortunately, the treatment has not been tested enough to be widely available, but it awaits further experimentation.

Giving Ourselves A Little Boost to Fight Cancer: Cell Therapy

New developments made in cancer research have opened new avenues of interest, namely cell therapy treatment. Under Dr. Carl June, new cancer treatments have seen great success. While now only effective against certain leukemia and lymphoma cases, Dr. June's new therapy has proved to be a momentous step in cancer treatment and the field of cell therapy.

Dr. June aims to present patients with enhanced versions of their own immune system, genetically engineering T-cells from patients to become "cancer cell serial killers," a single engineered T-cell being capable of killing up to 100,000 cancer cells. To date, the number of patients treated with cell therapy has only reached the hundreds, mainly due to the fact that the treatment process (outlined in the attached New York Times article) is developed for an individual, not a population. This, coupled with the limited range of cancers against which the treatment is efficient, may make it difficult to mainstream the treatment as a reliable option. Nevertheless, Dr. June and his team at the National Cancer Institute continue their work in cell therapy to make the treatment better and easier to use for the general populace.

If you're interested in reading more about this, here's a link to the NY Times article on it.


Slowing Cancer: DFMO

There are some really exciting developments in the area of cancer treatment.  One of them, that I want to share with you, is the drug Difluoromethylornithine (DFMO), a cytostatic inhibitor of cellular proliferation. DFMO prevents cancerous cell growth by interfering with ornithine decarboxylase, a key enzyme in cancerous metastasis.

Metastasis, the spread of cancer cells from one part of the body to many, is initiated when cancer cells escape from their starting point (ex: small intestine) into the bloodstream. This initiation is known as the epithelial-mesenchymal transition (EMT), in which cancer cells transition from their confined, epithelial state to their acute, mesenchymal state. During this transition, cancer cells also lose adhesion with each other, each becoming more mobile as an individual cell. You can see how this would be a huge challenge in the treatment of cancer. The more diffuse these cells become, the greater the spread of the cancer. EMT occurs once cells replicate enough and begin to invade the bloodstream, making treatment of the cancer much more difficult.

This is what makes DFMO such an exciting new development in cancer treatments. It works to inhibit cancer cell growth, thus making it a viable candidate in delaying the EMT in cancer patients. The use of DFMO in early stage cancer treatment (except cancer cell-suspensions like leukemia and lymphoma) would restrict the cells to a small tumor in a confined area. This would give doctors a chance to attack and remove the isolated tumor with cytotoxic (cell-killing) drugs and/or surgical methods. This would drastically drop the threat of a possible EMT and subsequent metastasis. Now tested on select groups of humans, DFMO has shown to be promising, its only downside being slight hearing loss (ototoxicity). Perhaps in the near future, DFMO will be used in initial stages of cancer treatments and decrease the ongoing spread of the disease.