MEDICAID
Medicaid Expansion & Mortality Among Patients With Breast, Lung & Colorectal Cancer
In states that have expanded Medicaid availability as part of the Affordable Care Act (ACA), mortality rates for three major forms of cancer are significantly lower than in states that have not expanded their Medicaid, a new study shows (JAMA Netw Open 2020; doi:10.1001/jamanetworkopen.2020.24366). Data from the study suggest the improvement in mortality results from cancers being diagnosed at an earlier stage in states with Medicaid expansion. Early detection of cancer is often critical to successful treatment of the disease. For the study, researchers used the National Cancer Database to track 523,802 patients across the country who were newly diagnosed with breast, lung, or colorectal cancer from 2012 through 2015. They compared mortality rates for these patients in states that expanded their Medicaid programs and those that did not. Twenty-four states and the District of Columbia expanded their programs on Jan. 1, 2014. If the 2 percent reduction was achieved in all states with expanded Medicaid, then among the approximately 69,000 patients diagnosed with cancer in those states, 1,384 lives would be saved yearly, researchers calculated. The biggest difference between the two groups was in patients whose cancers hadn't reached a metastatic stage and are considered curable. When investigators adjusted for the stage at which cancers were diagnosed, improvements in mortality were no longer seen-whether between expansion and non-expansion states or between the pre-expansion and post-expansion period. This suggests that the decline in mortality associated with Medicaid expansion is a byproduct of diagnosing cancer at an earlier stage. The investigators also found that the decrease in mortality in Medicaid expansion states occurred across population groups.
PANCREATIC CANCER
A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer
A preclinical study reports marked and lasting tumor regression in a mouse model, using a highly selective, potent, engineered antibody-drug combination (Adv Sci 2020; https://doi.org/10.1002/advs.202002852). The lab developed an antibody-drug conjugate (ADC) consisting of two parts: an antibody that selectively homes to ICAM1 on the surface of pancreatic cancer cells, and a drug toxic to cancer cells. Cells bearing ICAM1 on their surface are killed by the drug, while normal cells are spared. The team chose ICAM1 as a target for the ADC antibodies after screening the tumor surface for dozens of different proteins. The team performed similarly unbiased screening to select the best drug to include in the ADC from a pool of drugs already used clinically. They tested four candidate ADCs in two human pancreatic cancer cell lines, as well as in normal pancreatic cells. ADCs combining ICAM1 antibodies with the cytotoxic drug DM1 (mertansine), used clinically in HER2-positive breast cancer, were the most effective in killing tumor cells, working better than other ADC drugs. The DM1-ICAM1 antibody combination did not harm non-cancerous pancreatic cells, which do not produce ICAM-1. The team next randomized mice with pancreatic tumors to receive one of four treatments, given as systemic injections: the DM1-ICAM1 antibody conjugate, DM1 bound to a non-targeting antibody (IgG), gemcitabine (a first-line chemotherapy drug used in pancreatic cancer), or a sham treatment. Compared with the other groups, mice receiving the DM1-ICAM1 antibody conjugate had a significant reduction in tumor size that persisted during the 14-week study, even after just two doses. The treatment also effectively inhibited metastasis to normal organs, including lung, liver, and spleen. There was no observed toxicity, assessed by weighing the animals and through pathology analysis of their organs. Finally, researchers developed an MRI-based molecular tumor imaging technique to complement ICAM1 ADC therapy, confirming the presence of ICAM1 on the tumor without the need for an invasive biopsy.
PROTEINS
Large-Scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines
Through large-scale profiling of protein changes in response to drug treatments in cancer cell lines, researchers have generated a valuable resource to aid in predicting drug sensitivity, understand therapeutic resistance mechanisms, and identify optimal combination treatment strategies (Cancer Cell 2020; https://doi.org/10.1016/j.ccell.2020.10.008). Their findings include expression changes in more than 200 clinically relevant proteins across more than 300 cell lines after treatment with 168 different compounds, making it the largest dataset available on protein responses to drug treatments in cancer cell lines. To profile protein perturbations, the researchers used a reverse phase protein array (RPPA). Protein levels were measured at baseline and after treatment, often at multiple time points. The study evaluated drugs targeting a variety of signaling pathways and cellular processes across 319 commonly used, well-characterized cell lines from many cancer types, including breast, ovarian, uterine, skin, prostate, and hematologic cancers. Rather than analyzing all possible drug-cell line combinations, the researchers focused on those most likely to be relevant to the field. In total, they generated RPPA profiles of 15,492 samples, including 11,884 drug-treated samples and 3,608 control samples. The data was highly reproducible and verified by multiple independent pathways. The data obtained from these analyses provides important insight into the mechanisms of drug response or resistance, highlighting signaling pathways that are activated or suppressed following treatment with a given drug. Further, having data on both baseline and post-treatment protein levels is much more useful in modeling to predict sensitivity to additional drugs, the researchers said. The researchers also constructed a comprehensive map of protein-drug connections to visualize responses and better study relationships between different proteins and signaling pathways. The maps showcase which proteins have significant changes from a given drug, which drugs yield similar responses, and which proteins saw similar patterns of change. Studying these complex relationships can reveal unknown connections and point to potentially effective therapeutic combinations. Although the study includes only a subset of cancer types, the researchers hope to continue adding to the dataset in the future. In the long-term, the research team anticipates that proteomic profiling at baseline and following treatment may be a useful tool in clinical trials to better follow patient treatment responses and optimize therapeutic strategies.
GENETIC TESTING
Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome
In a new study, scientists conducted genetic testing in more than 3,000 patients who were diagnosed with cancer (JAMA Oncol 2020; doi:10.1001/jamaoncol.2020.6252). In all, the scientists found that 1 in 8 patients with cancer had an inherited cancer-related gene mutation. This mutation would not have been detected in half of these patients using a standard guideline-based approach. In the 2-year INTERCEPT study, Mayo Clinic provided free genetic testing and counseling to 3,084 patients as part of their standard cancer care. The project, representing the largest known multicenter study of universal testing of patients with cancer, included a broad mix of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers. The researchers were surprised to find that the standard guidelines physicians relied on to determine which patients with cancer should undergo genetic testing were only able to identify 48 percent of the patients with an inherited genetic mutation. During the study, when the researchers examined the effects of a genetic mutation discovery, they found that one-third of the patients with the highest-risk cancer genes had a change in their medical management, including the type of surgery or chemotherapy they received. All blood-related family members of patients found to have a genetic mutation were offered free genetic testing. Overall, 1 in 5 of these family members underwent testing.