Microfluidic Device is New Key Toward Tailored Anti-Cancer Treatment
등록일 2019년 01월 07일 목요일
수정일 2017년 11월 02일 목요일

Photo By science photo via Shutterstock

Researchers at the Purdue University developed a new technology that simulates the chemical process and reaction of tumors to chemotherapy drugs.It is a possible tool for screening anticancer drugs before approving them for treatment.

"There are many different types of chemotherapy drugs, so clinicians may be able to narrow down which ones are likely to be more effective than others.Successful drug delivery and overcoming drug resistance are the primary clinical challenges for management and treatment of cancer.To address this problem, we developed the tumor-microenvironment-on-chip (T-MOC)," said Bumsoo Han, a professor of mechanical and biomedical engineering at Purdue University.

The new microfluidic device has a size of 4.5-centimeter square with channels where cancer cells were cultured in a three dimensional called extracellular matrix, a scaffold-like material commonly found between cells in living tissue.The study also included interstitial fluid, a solution that bathes and surrounds the tissue cells found in tumor cells which have been thought as a drug delivery barrier.

Using the new technology could promote precision medicine for tailored anti-cancer treatment on patients and specific cancer types.Precision medicine is preferred by some clinicians in treating specific cancers that resist anticancer drugs.These cancer cells can produce multi-resistance proteins that expel active ingredients of chemotherapy out of their system to survive treatment.

The research team already proved that the T-MOC device was able to detect different types of cancer cells.In the new findings, the researchers showed that the device performed as well as research mice in testing anti-cancer drug effectiveness on two types of breast cancers.Additionally, the T-MOC achieved the plasma clearance, a body response from the liver and kidney to filter anti-cancer drugs, allowing a small amount of the drug to reach the tumor.The experiment allowed the researchers understand the effectiveness of anti-cancer drugs on the cellular level, and, as earlier stated, can be useful for testing anti-cancer drugs for specific cancer types before patient treatment.The study will continue to test other types of cancers such as pancreatic and prostate cancers.

"This confirms T-MOC's predictive ability for in-vivo drug response.This initial characterization of T-MOC indicates its transformative potential for testing drug effectiveness," said Han.

Photo By jovan vitanovski via Shutterstock

Drug-Resistance Evolution of Cancer Cells

Cancer cells developed methods to avoid anti-cancer drugs from killing them.These methods can stop medicinal effects of chemotherapy and even cytotoxic agents that kill any cells indiscriminately.Bill Murray, a retired major league baseball administrator, diagnosed with melanoma endured three separated courses of a new class of immunotherapy to treat the disease.

In 2011, Murray was first given a peptide-based vaccine and a monoclonal antibody called nivolumab.Nivolumab targets the programmed cell death protein 1 displayed on the surface of T-cells, a type of lymphocyte white blood cell.PD-1 works as a signal receptor on activated T-cells that packs down T-cell activity after detecting its counterpart, PD-L1 on the surface of tumor cells.The nivolumab was intended to block PD-L1 and allow Murray's T-cells to fight cancer.

Unfortunately, the treatment did not work and Murray had to be given a new antibody called ipilimumab.It binds cytotoxic T-lymphocyte-associated protein 4 expressed by PD-1 T-cells.The ipilimumab allowed Murray's immune system via T-cell offensive to combat cancer.

But five years later, Murray's cancer resurfaced and his oncologist, Dr.Jeffrey Weber at the New York University, needed to use a combination of nivolumab and ipilimumab to combat the disease.For the past nine months in 2016, Murray received four doses of the antibody combo drug and will need to continue until he completes the 12-month course.

Murray's experience is an example how cancer adapted to anti-cancer drugs that pinned many oncologists and forced them to develop new strategies to treat the disease.

"The big question is whether it's the tumor cells that are becoming resistant, if the immune system is becoming dysfunctional, or a combination of both," said Dr.Jesse Zaretsky, an MD and PhD student at the University of California.

In January this year, Dr.Charles Sawyers of the Memorial Sloan Kettering Cancer Center in New York, along with his colleagues, found a mechanism that allowed a tumor to bypass a molecular-targeted therapy.The tumor can change its identity through a mutation that made the therapy ineffective against it.

Scientists around the world are looking into how cancer develops resistance against anti-cancer drugs and how cancer invades the body on a cellular level.Nanotechnology, molecular-targeted therapies, and improvements to liposomal drug delivery system are under research to develop a better treatment for cancer.

- In 2050, about 8.2 million people will die caused by drug-resistant cancer, according to Statista.

- In 2020, there will be an expected increase of 630,000 cancer deaths per year from the 575,000 per year in 2010, according to the Center for Disease Control and Prevention.

- Melanoma, prostate, kidney, liver, and bladder cancers cases in men were expected to rise in 2010, according to CDC.

- Lung, breast, uterine, and thyroid cancer cases in women were expected to rise in 2010, according to CDC.

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