Overcoming Resistance

While a variety of cancer therapies and treatments exist, excluding those currently being researched or in clinical trials, a majority of these fail to prevent patient deaths due to drug resistance.

Despite the major improvements in cancer treatment over the past few decades, any successful cure to cancer still relies upon early cancer detection along with local therapy using surgery and radiotherapy. In the case that cancer is not discovered in the body, these cancer cells spread throughout the body and form metastases or what we know as tumors. At this point, the prognosis for cancer patients look grim with survival rates after five years falling below 20%.

Part of the problem is that most cancers have what is known as intrinsic resistance, which means the malignant cancer fails to respond to therapy during the time of diagnosis. Others instead have acquired resistance, wherein initial therapies may look promising and result in some benefits, but fail in the long-term due to the cancer cells developing a resistance.

But new research could improve these survival rates by paving the way for patient-tailored combinations of drugs—custom-made cocktails of therapies that would be more effective in alleviating the symptoms of cancer patients as well as eradicating therapy-resistant cancers.

Specifying the Targets
Credit: FIMM

One of the most important resistance mechanisms in cancer cells is the action of ATP-binding cassette transporters, drug pumps that basically deflect anti-cancer drugs away from cancer cells. Specifically, the most relevant is ABCB1—also called multi-drug resistance gene 1 (MDR1). However, previous attempts at targeting ABCB1 in anti-cancer therapies have been utter failures.

The most notable reason for this is that ABCB1 is present at many sites in the body aside from that of cancer cells—particularly at tissue barriers such as the gastrointestinal barrier and the blood-brain barrier. In other words, they have a crucial role in the day-to-day functioning of the human body.

So this has caused previous attempts at inhibiting ABCB1 to affect the body distribution of many different drugs and food components. While these agents inhibited ABCB1 from interacting with anti-cancer drugs on cancer cells, the nonspecific nature of these agents also led to toxic side effects.

Now, researchers have developed ABCB1-inhibitors that specifically target the transport of certain anti-cancer drugs, and does not affect their role in the distribution of other drugs and food. This means that future treatments could be tailored in such a way that anti-cancer cocktails are able to target cancer tumors and overcome drug resistance without causing any of the previous unwanted side effects.

While this research may take a few more years before it translates into actual therapies for cancer patients, it would be more than enough to provide a glimmer of hope for defeating cancer's menace.

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