September 23, 2020
Study finds AI can categorize cancer risk of lung nodules
Computed tomography scans for people at risk for lung cancer lead to earlier diagnoses and improve survival rates, but they can also lead to overtreatment when suspicious nodules turn out to be benign. A study for which Pierre Massion, MD, was the lead author published April 24 in American Journal of Respiratory and Critical Care Medicine indicates that an artificial intelligence strategy can correctly assess and categorize these indeterminate pulmonary nodules (IPNs). When compared to the conventional risk models clinicians currently use, the algorithm developed by the team of researchers in a very large dataset (15,693 nodules) reclassified IPNs into low-risk or high-risk categories in over one-third of cancers and benign nodules. Currently, clinicians refer to guidelines issued by the American College of Radiology and the American College of Chest Physicians. Adherence to these guidelines can be variable, and how patient cases are classified can be subjective.
Study explores melanoma drug’s effectiveness
A study by Ann Richmond, PhD, and colleagues supports the clinical development of a new second-line treatment for metastatic melanoma. The potential treatment, KRT-232, inhibits a gene that promotes tumor formation. Researchers demonstrated that KRT-232 significantly slowed the growth of tumors in mice resulting from patient-derived xenografts. The drug inhibits the protein MDM2 from degrading the cancer-fighting protein P53. The findings from the study were published March 31 in Clinical Cancer Research. While 60% of melanoma patients initially respond to immunotherapies, many patients end up in need of a second-line treatment.
Potential new cancer target
The role of transforming growth factor beta (TGF-beta) in cancer progression is still not fully understood due to its context-dependent biology. For a number of years, the laboratory of Sergey Novitskiy, MD, PhD, has studied how the nucleoside adenosine, which is essential for many cellular functions, contributes to actions of TGF-beta, including its tumor-driving effects. This is important as small molecule inhibitors of adenosine signaling are currently under consideration for anticancer immunotherapy. Reporting April 20 in the journal Cancer Research, Novitskiy and his colleagues demonstrated that expression of adenosine receptors correlates with collagen production and associates with lower survival in triple negative breast cancer patients.
Meat intake and colorectal polyps
Conventional colorectal adenomas are the precursor lesions for most colorectal cancers. In addition to these adenomas, other colorectal polyps are detected during colonoscopy. Sessile serrated polyps (SSPs) represent an alternative pathway to carcinogenesis that may account for 20-30% of colorectal cancer. Because a diagnostic consensus for SSPs was not reached until 2010, few epidemiologic studies have evaluated risk factors for SSPs. Martha Shrubsole, PhD, and colleagues have now evaluated intakes of meat, meat cooking methods and inferred meat mutagens with SSP risk in the Tennessee Colorectal Polyp Study. They report June 1 in the American Journal of Clinical Nutrition that the highest intakes of red meat, processed meat, well-done red meat and a particular meat-derived mutagen were strongly associated with increased risk of SSPs. SSP risk was increased in comparison to adenomas and hyperplastic polyps.
One-two punch for cancer
Many cancer cells evade critical DNA surveillance and maintenance by increasing the export — by the Exportin-1 (XPO1) nucleo-cytoplasmic transport protein — of nearly all major tumor suppressor proteins from the nucleus. Thus, overexpression of XPO1 is often an indicator of poor prognosis in numerous malignancies. Evasion of apoptosis, programmed cell death, is another cancer hallmark. While studies of venetoclax, a potent and selective inhibitor of the anti-apoptotic protein BCL2, have revealed impressive response rates, some aggressive hematologic malignancies escape through another anti-apoptotic protein, MCL1. Noting that both BCL2 and MCL1 expression are controlled by an XPO1-regulated protein, and that XPO1 is inactivated by SINE (selective inhibitor of nuclear export) compounds, Michael Savona, MD, and colleagues tested a combination of venetoclax and SINE compounds. Reporting Feb. 11 in the journal Blood Advances, they showed the combination enhanced cell killing in both in vitro and in vivo models of aggressive hematologic malignancies. Michael Byrne, DO, currently is leading a clinical trial to test this approach in patients.