publication date: Apr. 6, 2018

Clinical Roundup

NIH completes in-depth genomic analysis of 33 cancer types

Researchers funded by the NIH have completed a genomic analysis, known as the PanCancer Atlas, on a data set of molecular and clinical information from over 10,000 tumors representing 33 types of cancer.

The PanCancer Atlas, published as a collection of 29 papers across a suite of Cell journals, sums up the work accomplished by the Cancer Genome Atlas, a collaboration initiated and supported by the NHGRI and NCI, both part of NIH. The program, with over $300 million in total funding, involved upwards of 150 researchers at more than two dozen institutions across North America.

The project focused on cancer genome sequencing, and different types of data analyses, such as investigating gene and protein expression profiles, and associating them with clinical and imaging data.

The PanCancer Atlas is divided into three main categories, each anchored by a summary paper that recaps the core findings for the topic. The main topics include: cell of origin, oncogenic processes, and oncogenic pathways. Multiple companion papers report in-depth explorations of individual topics within these categories.

In the first summary paper, the authors summarize the findings from a set of analyses that used a technique called molecular clustering, which groups tumors by parameters such as genes being expressed, abnormality of chromosome numbers in tumor cells, and DNA modifications. The paper’s findings suggest that tumor types cluster by their possible cells of origin, a result that adds to our understanding of how tumor tissue of origin influences a cancer’s features and could lead to more specific treatments for various cancer types.

The second summary paper presents a broad view of the TCGA findings on the processes that lead to cancer development and progression. Specifically, the authors noted that the findings identified three critical oncogenic processes: mutations, both germline and somatic; the influence of the tumor’s underlying genome and epigenome on gene and protein expression; and the interplay of tumor and immune cells. These findings will help prioritize the development of new treatments and immunotherapies for a wide range of cancers.

The final summary paper details TCGA investigations on the genomic alterations in the signaling pathways that control cell cycle progression, cell death and cell growth, revealing the similarities and differences in these processes across a range of cancers.

 

Simultaneous chemo and immunotherapy may be better for some metastatic bladder cancers

Researchers from Mount Sinai and Sema4, a health information company and Mount Sinai venture, discovered that giving metastatic bladder cancer patients simultaneous chemotherapy and immunotherapy is safe and that patients whose tumors have certain genetic mutations may respond particularly well to this combination approach, according to the results of a clinical trial published in European Urology.

Though chemotherapy and immunotherapy have become standard options for the treatment of metastatic bladder cancer, it was previously unknown whether these therapies could be given together and whether chemotherapy’s side effect of weakening the immune system would inhibit immunotherapy.

The phase II trial was conducted at six cancer centers, and patients in the trial did not show any additional or more severe side effects than patients given chemotherapy or immunotherapy alone, a finding that showed the combination therapy is a safe alternative.

Researchers also generated evidence showing that immunotherapy could boost immune cells in the blood of patients receiving concurrent chemotherapy, allaying previous concerns that chemotherapy might counteract the effects of immunotherapy.

One of the new trials, which Matthew Galsky, director of genitourinary medical oncology and professor of urology, medicine, hematology and medical oncology at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and principal investigator of the study.

The study, headed by Galsky at Mount Sinai and other centers, gives chemotherapy and immunotherapy to a subset of patients with earlier-stage bladder cancer to determine if this combination can head off the need for surgery to remove the bladder, a standard treatment but one with quality-of-life-altering implications that include wearing a urostomy bag outside the body to collect urine. The other trial combines two different chemotherapy regimens with immunotherapy to determine the best types of chemotherapy drugs to combine with immunotherapy.

Galsky and Andrew Uzilov, director of cancer genomics for Sema4, and Huan Wang, Sema4 bioinformatics scientist, and other researchers hypothesized that patients with tumors with particular genetic mutations might respond best to the combination of chemotherapy and immunotherapy.

They found that certain types of mutations in DNA damage response genes were associated with better response to the combined chemotherapy and immunotherapy. If validated in subsequent studies, these findings could add a novel biomarker to the “precision oncology toolbox” and refine the selection of patients who might benefit from concurrent administration of chemotherapy and immunotherapy.

This study was supported by Bristol-Myers Squibb, Cancer Research Institute Clinical Strategy Team Grant, and National Cancer Institute grant P30 CA196521.

Copyright (c) 2018 The Cancer Letter Inc.