Chemotherapy can speed up cancer spread, Chinese study finds | Victoria Bela, South China Morning Post Common treatment can wake up dormant cancer cells, causing the disease to spread from original sites to other organs, team discovers A team of Chinese scientists has found that the spread of cancer from original tumour sites to distant organs can be caused by chemotherapy triggering the awakening of dormant cancer cells. Their findings shed light on why breast cancer patients can experience cancer metastasis in organs like the lungs despite successful treatment of their primary tumours. The team also found that the use of specific drugs in combination with chemotherapy could be used to inhibit this process in mice, and a clinical trial is already under way in breast cancer patients. “We demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells,” the team wrote in a paper published in the peer-reviewed journal Cancer Cell on July 3. “This study provides direct evidence of dormancy awakening and reveals a mechanism underlying [the] detrimental effect of chemotherapy on metastasis, highlighting potential strategies to improve cancer treatment.” Researchers in the United States previously found that high doses of radiation therapy to treat cancer could paradoxically lead to the growth of metastatic tumours. Many patients who undergo chemotherapy to treat primary tumours, the original tumour site in the body where cancer cells first start to develop, can have cancer relapses in other organs even after complete primary tumour regression. This has led to research into whether chemotherapy can have a similar paradoxical effect, in which it both treats primary tumours and triggers cancer metastasis. “It is postulated that the reactivation, or awakening, of dormant disseminated tumour cells (DTCs) in distant organs results in metastatic relapse after the asymptomatic period,” the team said. Studies have shown that disseminated cancer cells, which travel from primary tumours to sites in the body, can be found even during the early stages of primary cancer formation, according to a news release by the Chinese Academy of Sciences (CAS). These cells can stay in a dormant state for years, during which they do not grow and multiply, allowing them to evade chemotherapy. Researchers have previously identified molecular mechanisms that regulate metastatic relapse and disseminated cancer cell dormancy. However, it has not been clear whether metastasis results from the reactivation of dormant cells or the growth of rare, non-dormant disseminated cells. “Understanding the exogenous causes of DTC awakening will help disease management of cancer survivors, offering opportunities to prevent and interrupt metastatic relapse after initial therapies,” the researchers said in their paper. To study this, the team led by Hu Guohong, a professor at CAS’ Shanghai Institute of Nutrition and Health, along with researchers from Fudan University and Qilu Hospital of Shandong University, developed a cancer cell dormancy tracing approach. The team confirmed that chemotherapy-induced reactivation of dormant cells from breast cancer could lead to metastatic relapse in the lungs of mice. Their findings demonstrated that the “awakening of dormant DTCs, but not accumulation of pre-existing proliferative DTCs, is responsible for metastases induced by chemotherapy”. Chemotherapy induces senescence – an accelerated state of ageing in which cells stop multiplying and release inflammation-causing chemicals – in specialised connective tissue called fibroblasts. The team found that senescent fibroblasts release proteins that cause immune cells called neutrophils to form weblike formations, called neutrophil extracellular traps, which change the environment in the lung into one that helps dormant cancer cells restart their growth. The remodelling of the extracellular matrix, a complex network of molecules that support and surround cells, also degrades tumour-suppressing factors. “We explored if chemotherapy-induced senescent fibroblasts could be a therapeutic target to improve the effect of chemotherapy on metastasis inhibition,” the team said. The researchers discovered that combining senolytic drugs, which eliminate senescent cells, with the chemotherapy drug doxorubicin reduced senescent fibroblasts in the lungs of mice. “Since the senolytics have shown acceptable safety profiles and benefits in clinics, this could be a promising strategy and warrant further clinical investigation,” they said. The team said that, based on these study results, a phase II clinical trial was under way to explore the safety of combining the senolytic drugs dasatinib and quercetin with chemotherapy to treat triple-negative breast cancer. Read more: archive.is/bQdIz