Biologists at University of Texas have engineered new molecules that could potentially stall lung cancer by starving the cancer cells of food.
Cancer cells grow faster when they have access to heme—that’s the oxygen-binding in haemoglobin, according to a preclinical study on mice published in the journal Cancer Research.
Expansion of lung tumours in mice slowed when access to heme was restricted, Dr Li Zhang and her team showed in the study.
The new molecule engineered by two of her graduate students in the department of biological sciences suggest a potential new path forward in treating non-small cell lung cancer—by starving the cells of heme.
Zhang joined the university in 2007 and began working on lung cancer in 2013.
“In that time, our results have convincingly shown the relevance of heme to this disease,” she said.
“It’s fascinating how tumor cells take advantage of their environment,” Zhang said. “The lungs are so rich in oxygen. But you need heme to use it.”
The team emphasized that its potential treatment approach is designed to work in tandem with chemotherapy or other forms of cancer remedy, not by itself.
“This method wouldn’t kill tumors; it would delay their growth,” Zhang said. “So it would not be a stand-alone treatment, but it could replace less effective forms of therapy that rely on inhibition of angiogenesis — the creation of new blood vessels.”
Zhang’s new results emphasize that tumors create energy using molecules other than glucose — a type of sugar known since the 1920s to feed tumors. Where more heme is being made, more oxygen is consumed to make more adenosine triphosphate (ATP) — the energy-carrying molecule that fuels many activities in living cells. Take the heme away, and cancer cell growth slows down.
“Years ago, it was believed that cancer cells did not use oxygen, only glucose, to make energy,” Zhang said. “Now we know that most cancer cells use oxygen, and this type of lung cancer cell is an example. It oxidizes the glucose to generate energy much more efficiently, manufacturing about 30 ATP molecules per glucose molecule.”
Sagar Sohoni and Poorva Ghosh, co-first authors of the study and doctoral students in Zhang’s lab, collaborated to investigate how a series of engineered molecules deny heme to cancer cells.
Zhang said that these heme-sequestering peptides, or HSPs, are able to “hijack” heme from the spaces between cells, where tumors would be able to access it, while leaving alone the heme in healthy cells.
“Heme sequestering doesn’t adversely affect the normal cells,” Zhang said. “They synthesize the little heme they need on their own. Also, our peptide won’t go into cells so it shouldn’t provoke many side effects.”
Demonstrating the reduced progress of heme-starved cancer cells makes a compelling case on its own. To hammer the point home, Zhang’s team modified NSCLC cells to allow them to obtain heme faster. Those cells behaved as expected — aggressive and invasive, consuming oxygen quickly and cranking out more ATP.
“Cancer cells’ energy demands are very high compared to the normal cells around them,” Zhang said. “When more heme is available, NSCLC cells grow and reproduce at an alarming rate.”
The next step is to continue refining the design of the HSPs to create a version for use in humans, “further optimizing its efficacy while continuing to prove that its toxicity is low,” Zhang said.
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