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Friday 28th October 2016

Chemo can make tumours grow bigger

7th August 2012

Chemotherapy, a key weapon in the fight against cancer, may actually spur the growth of tumours, according to new research from the United States.


The drugs used in chemotherapy can prompt healthy cells in the vicinity of tumours to release a compound that stimulates cancer to grow even bigger, according to a report in the journal Nature Medicine.

The process eventually leads to resistance to treatment on the part of the tumour, according to senior study author Peter S. Nelson, of the Human Biology Division at the Fred Hutchinson Cancer Research Center in Seattle.

According to Nelson, cancer cells inside the body live in a very complex microenvironment or neighbourhood. This means that the location of a tumour cell and what constitutes its neighbours influences its response and resistance to therapy.

In cases of advanced cancer, chemotherapy fails at the point where increased doses of drug needed to kill the tumour would also kill the patient.

He said petri dish cancer cells can be "cured" by huge doses of toxic chemotherapy, but that high doses of chemotherapy in humans will kill off healthy cells as well as tumours.

Chemotherapy targeting common, solid tumours, therefore, is given as smaller doses divided into cycles so as to give healthy tissue time to recuperate.

However, any tumour cells that do survive then become resistant to the drugs used in subsequent cycles of chemotherapy.

Nelson's team looked at one particular type of normal cell, a fibroblast, that is found near cancer tumours, and helps maintain connective tissue, holding other types of cells and tissue together, acting like a framework for other cells.

Fibroblasts, which play a part in the healing of wounds, and which produce collagen, can behave in unusual ways if their DNA is damaged, however, and release a number of compounds aimed at stimulating the growth of cells.

Specifically, when damaged in the process of chemotherapy, fibroblasts produce a protein called WNT16B around the cancer cells, which can stimulate the cancer to grow when it reaches high enough concentrations.

The tumour will then grow, invade the surrounding healthy tissue and develop resistance to chemotherapy, Nelson told a news conference.

Some of the fibroblasts produced 30 times as much WNT16B protein under chemotherapy as normal, a result the researchers said was "completely unexpected."

According to Fran Balkwill, an expert on tumour microenvironments at Cancer UK, the study confirmed earlier results showing that cancer treatments target cells in and around tumours.

This effect can sometime be helpful, for example, when healthy immune cells are triggered by chemotherapy to attack cancer cells.

But now that Nelson's team had confirmed that healthy cells surrounding the tumour can also help the tumour to become resistant to treatment, the next step should be to find ways to target these resistance mechanisms, thereby boosting the effectiveness of chemotherapy, Balkwill said.

Cancer approaches increasingly use a precise "sniper" approach to target certain molecules, rather than damaging DNA in tumours.

The microenvironment can play a crucial role in the success or failure of such treatments, Nelson's team concluded.


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