‘Junk DNA’ No More: Johns Hopkins Investigators Develop Method of Identifying Cancers from Repeat Elements of Genetic Code

Repeats of DNA sequences, often referred to as “junk DNA” or “dark matter,” that are found in chromosomes and could contribute to cancer or other diseases have been challenging to identify and characterize. Now, investigators at the Johns Hopkins Kimmel Cancer Center have developed a novel approach that uses machine learning to identify these elements in cancerous tissue, as well as in cell-free DNA (cfDNA) — fragments that are shed from tumors and float in the bloodstream. This new method could provide a noninvasive means of detecting cancers or monitoring response to therapy. Machine learning is a type of artificial intelligence that uses data and computer algorithms to perform complex tasks and accelerate research.

Combination Urothelial Cancer Treatment Nearly Doubles Patient Survival in International Trial

Combining the anticancer drugs enfortumab vedotin and pembrolizumab (EV+P) led to significantly improved survival rates among patients with advanced urothelial cancer (the most common type of bladder cancer) compared with standard chemotherapy, according to results of a large international clinical trial involving 185 sites, including the Johns Hopkins Kimmel Cancer Center’s Greenberg Bladder Cancer Institute, in 25 countries.

Immunotherapy Combination May Benefit Patients with Transplanted Kidneys and Advanced Skin Cancers

People who have had a kidney transplant are at high risk for developing skin cancers. New research directed by investigators from the Johns Hopkins Kimmel Cancer Center is exploring the best combination of treatments to target skin cancers while preserving the transplanted organs.

Transcription Factor Plays Pivotal Role in Right-Sided Colon Cancers

The colon is often thought of as one organ, but the right and left parts of the colon have different molecular features in cancers. New research in mice from investigators at the Johns Hopkins Kimmel Cancer Center demonstrates that these regions also have distinct transcriptional programs, or cellular processes, that regulate the development of normal and cancerous cells.

Immune Cell Receptor Provides Promising Immunotherapy Target

Drugs that target a receptor on immune cells called activin receptor 1C may combat tumor-induced immune suppression and help patients’ immune systems fight back against cancer, according to a study by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Age-Related Changes in Fibroblast Cells Promote Pancreatic Cancer Growth and Spread

Older people may be at greater risk of developing pancreatic cancer and have poorer prognoses because of age-related changes in cells in the pancreas called fibroblasts, according to research led by investigators from the Johns Hopkins Kimmel Cancer Center, the Johns Hopkins Bloomberg School of Public Health and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

A new pathologic scoring system that accurately assesses how much lung tumor is left after a patient receives presurgical cancer treatments can be used to predict survival, according to new research led by investigators at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center and the Mark Foundation Center for Advanced Genomics and Imaging at the Johns Hopkins University.

Capturing Immunotherapy Response in a Blood Drop

Liquid biopsies are blood tests that can serially measure circulating tumor DNA (cell-free DNA that is shed into the bloodstream by dying cancer cells). When used in patients with advanced non-small cell lung cancer undergoing immunotherapy, they may identify patients who could benefit from treatment with additional drugs, according to a phase 2 clinical trial in the U.S. and Canada. The trial is led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy, BC Cancer and the Canadian Cancer trials Group (CCTG).

Immune Checkpoint Blockade Prior to Surgery Promising in Multiple Cancer Types

Treating cancer with immunotherapies known as an immune checkpoint blockade (ICB) prior to surgery (so-called neoadjuvant immunotherapy) has been a rapidly growing area of research, but the scientific community is just scratching the surface of what is possible, according to a review article co-authored by several current and former investigators from the Bloomberg~Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins Kimmel Cancer Center.

Trial: Combination Immunotherapy Prior To Lung Cancer Surgery Appears Promising

Patients with stage 1–3 non-small cell lung cancer (NSCLC) given a combination immunotherapy prior to surgery (neoadjuvant) had a better major pathological response (10% or less residual cancer) when the cancer was removed than those who took a single immunotherapy agent alone, according to results of a novel multicenter phase 2 NeoCOAST platform trial that included two investigators from the Johns Hopkins Kimmel Cancer Center and its Bloomberg-Kimmel Institute for Cancer Immunotherapy. The results were published online Sept. 14 in Cancer Discovery, a journal of the American Association for Cancer Research.

New Machine-Learning Method May Aid Personalized Cancer Therapy

Deep-learning technology developed by a team of Johns Hopkins engineers and cancer researchers can accurately predict cancer-related protein fragments that may trigger an immune system response. If validated in clinical trials, the technology could help scientists overcome a major hurdle to developing personalized immunotherapies and vaccines.

Transcription Factors Contribute to Subtypes of Colorectal Cancers

New research in colorectal cancers directed by investigators at the Johns Hopkins Kimmel Cancer Center suggests that expression of transcription factors — proteins that help turn specific genes on or off by binding to nearby DNA — may play a central role in the degree of DNA methylation across the genome, contributing to the development of different subtypes of these cancers. Methylation is a process in which certain chemical groups attach to areas of DNA that guide genes’ on/off switches.

New Study at Johns Hopkins Kimmel Cancer Center Shows Patient/Clinician Identity Differences Are Factor in Cancer Care

A new study by researchers at the Johns Hopkins Kimmel Cancer Center in collaboration with Dell Medical School, University of Minnesota, and the Vanderbilt University Medical Center, using a national data sample from the National Institutes of Health All of Us Research Program, revealed that a small but statistically significant proportion of patients with cancer, especially younger and lower-income minorities, disproportionately reported delaying care because of patient/clinician racial, gender and cultural differences.

Novel Immunotherapy Agent Safe, Shows Promise Against High-Risk Prostate Cancers

A new drug, a monoclonal antibody known as enoblituzumab, is safe in men with aggressive prostate cancer and may induce clinical activity against cancer throughout the body, according to a phase 2 study led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Researchers Id Biomarkers of Response to Immunotherapy for Kidney Cancer

The number of immune cells in and around kidney tumors, the amount of dead cancer tissue, and mutations to a tumor suppressor gene called PBRM1 form a biomarker signature that can predict — before treatment begins — how well patients with kidney cancer will respond to immunotherapy, according to new research directed by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.

‘Hard to Lose’ Mutations in Tumors May Predict Response to Immunotherapy

Investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy have found that a subset of mutations within the overall TMB, termed “persistent mutations,” are less likely to be edited out as cancer evolves, rendering tumors continuously visible to the immune system and predisposing them to respond to immunotherapy.

DNA Shed From Colon Cancers Into Bloodstream Successfully Guides Chemotherapy After Surgery

A multi-institutional, international study, led by researchers at the Johns Hopkins Kimmel Cancer Center and WEHI in Melbourne, Australia, found that testing for ctDNA after surgery and directing chemotherapy to ctDNA-positive patients reduced the use of chemotherapy overall without compromising recurrence-free survival.

Johns Hopkins Medicine Researchers Awarded Nearly $8 Million from Break Through Cancer Foundation

The Johns Hopkins Kimmel Cancer Center and the Departments of Gynecology/Obstetrics, Neurosurgery and Pathology have been awarded more than $7.8 million for novel, multicenter projects designed to intercept and find cures for several deadly cancers, including pancreatic cancer, ovarian cancer, and the brain cancer known as glioblastoma.

Immunotherapy-Chemotherapy Treatment Coupled with In-Depth Genomic Analyses Leads to Improved Survival for Patients with Mesothelioma

Combining the immunotherapy agent durvalumab with the chemotherapy agents pemetrexed and cisplatin or carboplatin may provide a new treatment option for patients who have inoperable pleural mesothelioma, a cancer of the tissues lining the lungs, according to a phase II clinical trial led by researchers at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Studies Find B7-H3 Protein a Novel, Promising Target for Prostate Cancer Treatments

The immune checkpoint protein B7-H3 may be a promising new target for immunotherapy in treatment-resistant prostate cancers, according to two new studies led by researchers at the Johns Hopkins Kimmel Cancer Center. The studies were presented recently at the European Society for Medical Oncology (ESMO) 2021 Conference.

Astronomy Meets Pathology to Identify Predictive Biomarkers for Cancer Immunotherapy

Pairing sky-mapping algorithms with advanced immunofluorescence imaging of cancer biopsies, researchers at The Mark Foundation Center for Advanced Genomics and Imaging at Johns Hopkins University and the Bloomberg~Kimmel Institute for Cancer Immunotherapy developed a robust platform to guide immunotherapy by predicting which cancers will respond to specific therapies targeting the immune system.

Dual Immunotherapy Regimen Delays Cancer Progression in Patients with Advanced Melanoma

A treatment regimen for patients with advanced melanoma that combines the immunotherapy agents relatlimab (anti-LAG-3) and nivolumab (anti-PD-1) delayed time to cancer progression significantly more than nivolumab alone, according to results of a study to be presented June 6 at the 2021 American Society of Clinical Oncology (ASCO) annual meeting.

Software Package Enables Deeper Understanding of Cancer Immune Responses

Researchers at the Bloomberg Kimmel Institute for Caner Immunotherapy at the Johns Hopkins Kimmel Cancer Center have developed DeepTCR, a software package that employs deep-learning algorithms to analyze T-cell receptor (TCR) sequencing data. T-cell receptors are found on the surface of immune T cells. These receptors bind to certain antigens, or proteins, found on abnormal cells, such as cancer cells and cells infected with a virus or bacteria, to guide the T cells to attack and destroy the affected cells.

Researchers Develop New Method for Identifying Mutational Signatures in Cancer

Researchers at the Johns Hopkins Kimmel Cancer Center used machine learning techniques to detect mutational signatures in cancer patients. Their algorithm outperformed the current standard of analysis and revealed new mutational signatures associated with obesity, which is believed by cancer prevention experts to be becoming the most significant lifestyle factor contributing to cancer in the U.S. and most of the Western world.

Cancer Immunotherapy Approach Targets Common Genetic Alteration

Researchers developed a prototype for a new cancer immunotherapy that uses engineered T cells to target a genetic alteration common among all cancers. The approach, which stimulates an immune response against cells that are missing one gene copy, called loss of heterozygosity (LOH), was developed by researchers at the Ludwig Center, Lustgarten Laboratory and the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center.

Mutant Gene-Targeted Immunotherapy Approach Developed

Johns Hopkins Kimmel Cancer Center study co-author Bert Vogelstein, M.D., will present the related talk “Targeting genetic alterations in cancers with immunotherapeutic agents” at 11 a.m., March 1, at the Advances in Genome Biology and Technology (AGBT) conference. More information can be found at: https://www.agbt.org/events/general-meeting/agenda/. NOTE: AGBT provides complimentary press registration to staff and working freelance journalists who wish to cover the meeting. https://www.agbt.org/media/guidelines/

Story Tips from Johns Hopkins Experts on COVID-19

Vaccines take time to work. After getting a COVID-19 vaccine, it takes a while for the immune system to fully respond and provide protection from the virus. For the Moderna and Pfizer COVID-19 vaccines, it takes up to two weeks after the second shot to become appropriately protected.

Behaviors Surrounding Oral Sex May Increase HPV-Related Cancer Risk

A wide breadth of behaviors surrounding oral sex may affect the risk of oral HPV infection and of a virus-associated head and neck cancer that can be spread through this route, a new study led by researchers at the Johns Hopkins Kimmel Cancer Center suggests. These findings add nuance to the connection between oral sex and oropharyngeal cancer — tumors that occur in the mouth and throat — and could help inform research and public health efforts aimed at preventing this disease.

Research News Tip Sheet: Story Ideas from Johns Hopkins Medicine

During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every Tuesday throughout the duration of the outbreak.

Researchers Urge Clinical Trial of Blood Pressure Drug to Prevent Lethal Complication of Covid-19

Researchers in the Ludwig Center at the Johns Hopkins Kimmel Cancer Center report they have identified a drug treatment that could—if given early enough—potentially reduce the risk of death from the most serious complication of Coronavirus disease 2019 (COVID-19), also known as SARS-CoV-2 i

Immunotherapy Before Surgery Could Advance Care of an Aggressive Form of Skin Cancer

In what is believed to be a first-of-its-kind study to evaluate the safety of a type of immunotherapy before surgery in patients with an aggressive form of skin cancer, researchers report that the treatment eliminated pathologic evidence of cancer in nearly half of the study participants undergoing surgery. In patients whose tumors respond, this treatment approach offers the potential to reduce the extent of surgery and may also slow or eliminate tumor relapses that often occur after surgery.

Experiments in Mice And Human Cells Shed Light On Best Way to Deliver Nanoparticle Therapy For Cancer

Researchers in the cancer nanomedicine community debate whether use of tiny structures, called nanoparticles, can best deliver drug therapy to tumors passively — allowing the nanoparticles to diffuse into tumors and become held in place, or actively — adding a targeted anti-cancer molecule to bind to specific cancer cell receptors and, in theory, keep the nanoparticle in the tumor longer. Now, new research on human and mouse tumors in mice by investigators at the Johns Hopkins Kimmel Cancer Center suggests the question is even more complicated.

Combination Drug Therapy For Childhood Brain Tumors Shows Promise In Laboratory Models

In experiments with human cells and mice, researchers at the Johns Hopkins Kimmel Cancer Center report evidence that combining the experimental cancer medication TAK228 (also called sapanisertib) with an existing anti-cancer drug called trametinib may be more effective than either drug alone in decreasing the growth of pediatric low-grade gliomas. These cancers are the most common childhood brain cancer, accounting for up to one-third of all cases. Low grade pediatric gliomas arise in brain cells (glia) that support and nourish neurons, and current standard chemotherapies with decades-old drugs, while generally effective in lengthening life, often carry side effects or are not tolerated. Approximately 50% of children treated with traditional therapy have their tumors regrow, underscoring the need for better, targeted treatments.

Multimodal Genomic Analyses Predict Response to Immunotherapy in Lung Cancer Patients

Researchers at Johns Hopkins Kimmel Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy and the Johns Hopkins University School of Medicine have developed an integrated genomic approach that potentially could help physicians predict which patients with nonsmall cell lung cancer will respond to therapy with immune checkpoint inhibitors.