Over 1,300 scientists worked for a decade to sequence the genomes of 38 types of cancer in a global study called the Pan-Cancer Analysis of Whole Genomes Consortium. Though genetic sequencing for cancer is not a new feat for scientists, this project provided an “unprecedented” look into how genetic mutations can contribute to cancer. Scientists pinpointed 705 mutations associated with tumor growth and found that cancer growth resulted from an average of four or five mutations. These mutations are called “driver mutations” and theoretically, individually tailored treatment could target these mutations to stop tumor growth at its source.

Scientists also found that one third of these “driver mutations” happen years or decades before cancer is found in a clinical setting. In these cases, the window for treatment of the genetic mutations prior to the cancer’s growth is significantly larger than previously thought. Scientists could potentially use these findings to create diagnostic tests that could identify cancer much earlier than is currently possible. Identifying and targeting driver mutations has been the basis for cancer drug discovery for a number of years. Drugs such as imatinib and ponatinib target driver oncogenes such as BCR-ABL, while drugs like brigatinib and crizotinib target driver oncogenes known as ALK and ROS.

The information obtained in the study is transformational, with one BBC report saying that the results of the project “provide an almost complete picture of all cancers.” However, to truly have an impact on cancer patients, their lives and their families, the research has to translate into applicable diagnostic tools and treatment plans, which requires clinical information.

Clinical information, such as family history and therapies utilized in cancer treatment, has been largely left out of previous genome sequencing studies because patient information is difficult to access, expensive to obtain and risky for patient privacy. Despite its complexity, clinical information is necessary to move the needle on cancer detection and treatment. According to a Nature editorial, “the future of cancer genomics lies in the clinic.”

This huge step forward in cancer research leaves much to be discovered. In five percent of cases studied, no driver mutations were found, leaving scientists still searching for answers. If pre-cancer diagnostic testing becomes possible, medical providers will need to know how to differentiate between problematic and benign mutations. The transformational research of this project has laid the groundwork to answer these questions and better fight cancer.

A study conducted by researchers at the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard has shown that a variety of non-cancer drugs may also be effective as treatments for cancer. The study, which was published in the Nature Cancer journal, tested approximately 4,518 drugs against 578 cancer types and found almost 50 drugs showed some anti-cancer activity. This repurposing study is intriguing to scientists and doctors because the drugs have already been FDA-approved for safety, which means that the drugs could be accelerated into clinical trials for effectiveness against various types of cancer.

The drugs that were investigated through this study were previously used in medical areas vastly different than oncology. For example, one of the effective drugs is levonorgestrel, which is a hormonal drug used in birth control pills and emergency contraception. Also effective was disulfiram, which is used to treat alcohol dependence. The study was wide-ranging, aimed at giving researchers an understanding of which drugs could potentially be useful, or be modified to be effective, in oncology. This study is referred to as “repurposing” proven medicines from one indication to another.

The study also revealed previously unknown mechanisms for the studied drugs. For example, some of these drugs worked by activating or stabilizing existing proteins, which was effective against cancer even though most current cancer drugs work by blocking proteins. Most of the 49 drugs that did prove to have anti-cancer properties worked through a previously unidentified mechanism.

The discovery of unidentified mechanisms presents an additional opportunity for researchers. In addition to repurposing these into anti-cancer treatments, but they were also able to begin identifying other mechanisms that work against cancer that could inform new treatments for cancer. Understanding that activating or stabilizing a protein in some cases is effective against cancer opens up new avenues for brand new oncological drugs in addition to the repurposed treatments.

Overall, this repurposing study suggests an overall method to accelerate the development of new drugs to treat cancer. By finding which mechanisms work against cancer in other drugs, scientists will be able to create brand new drugs and push existing drugs into trials for effectiveness much more quickly. While this study did not produce any immediate cancer treatments, the information produced will help scientists push cancer research forward.

During the 4th of July week, the Children’s Hospital of Wisconsin admitted two teenage boys for difficulty breathing, fevers and a host of other symptoms. Their airways were irritated to the point of bleeding in some cases, but did not have any signs of common lung infections, like pneumonia. This reminded pulmonologist Dr. Lynn D’Andrea of another teenage boy who had been admitted in mid-June with similar symptoms. It was apparent to doctors in the pediatric unit that this was not anything they had seen before or a documented contagious infection. Looking into links between the boys, the only thing they all had in common was that they had vaped before.

Dr. D’Andrea and her colleagues became the first to report a deadly disease that would drive regulatory agencies, governing bodies and the Centers for Disease Control (CDC) to take action. E-cigarette, or vaping, product use associated illness (EVALI), can cause a variety of symptoms, including cough, shortness of breath, chest pain, nausea, vomiting, fever, chills and weight loss;
these symptoms can develop in as little as a few days or over several weeks. The illness has affected 2506 people, as of the Dec. 17, 2019 CDC report, including fifty-four associated deaths. While the disease appears to have peaked in September and declined in prevalence ever since, the CDC and healthcare providers remain vigilant.

On December 20, 2019, the CDC released a study that found a link between vitamin E acetate and EVALI. According to a study of bronchoalveolar lavage fluid (lung fluid) from 51 EVALI patients and 99 healthy people, vitamin E acetate was found in almost all of the EVALI fluid samples, but not in any of the healthy samples. Vitamin E acetate is found in THC-containing e-cigarettes because vitamin E acetate can be used as a cutting agent. This practice became common in the illicit market in 2019, aligning with the onset of EVALI cases.

Despite this breakthrough in the EVALI investigation, the CDC warns that there may be multiple causes of EVALI and other potential causes are still being investigated. The CDC cautions that any person using e-cigarettes should monitor for EVALI symptoms and see a healthcare professional immediately if any symptoms develop.

William G. Kaelin, Jr., MD, Sidney Farber Professor of Medicine at Harvard Medical School and the Dana Farber Cancer Institute, started work 15 years ago with an interesting bit of information about kidney cancer: patients with a mutation in the VHL gene (von Hippel Lindau syndrome) were much more likely to develop kidney cancer. Kaelin set out to figure out why and possibly
find a treatment for several cancers, including clear-cell renal carcinoma, a deadly form of kidney cancer.

Through his research, Kaelin found that the VHL gene regulates cell response to oxygen levels as well as another molecular factor, HIF, which is responsible for triggering the production of red blood cells and blood vessels based on oxygen supply. Cancer cells with mutated VHL genes can take advantage of this system to trick the body into building blood vessels straight to cancerous tumors, thus feeding their own growth with the body’s blood supply. This mutation in the VHL gene allows the tumor to hijack the HIFs and stimulate the production of the protein VEGF, which enables extra blood vessels to enhance blood supply directly to the tumor.

This discovery led to the production of VEGF inhibitors, which showed success in improving the chances for patients with renal cell carcinoma, a fatal kidney cancer with a median survival of one year. In 2019, Kaelin on two other renown scientists were awarded the Nobel Prize in Physiology or Medicine “for their discoveries of how cells sense and adapt to oxygen availability.”

The link between oxygen and cancer cells continues to be an area of interest for the medical field. Normal cells use HIFs to regulate oxygen supply based on external oxygen availability, but cancer cells use HIFs to increase blood supply and grow tumors. On the other hand, cancer cells without enough oxygen (hypoxic cells) can spread beyond their origin and resist cancer treatments. While it is clear that the use of oxygen (or lack thereof) by cancer cells is tied to cancer growth and treatment, the full story is the subject of ongoing research.

A group of physician-scientists conducted a study on the safety and efficacy of a new drug for patients with pyruvate kinase deficiency. This disorder is a rare type of anemia caused by a lack of pyruvate kinase, a key enzyme in red blood cell production and survival. According to the Dana-Farber Cancer Institute, there have been no disease-modifying treatments for the deficiency since the discovery of the disorder in the 1960s. Patients with pyruvate kinase
deficiency could only be treated for the symptoms of the disorder, most often with a splenectomy, cholecystectomy, and/or blood transfusions.

A study published in the New England Journal of Medicine has shown that the new oral drug, mitapivat, can raise hemoglobin levels in about half of study participants with pyruvate kinase deficiency. In a typical patient with this disorder, red blood cells break down in just a few weeks due to a lack of pyruvate kinase. Mitapivat works by activating this enzyme in red blood cells,
which helps prevent premature breakdown of the hemoglobin-carrying cells.

The breakdown of red blood cells and subsequent hemolytic anemia causes some patients to face severe complications, including gallstones, pulmonary hypertension, and cirrhosis. In addition, the medical procedures completed to relieve symptoms, such as splenectomies, have their own list of potential complications. Mitapivat provides an alternative by modifying the disease directly, rather than the symptoms of the anemia.

While mitapivat represents an important step forward in the treatment methodology for this rare genetic disease, further research needs to be conducted to determine the safety of the drug long-term and for children. Mitapivat also saw improvement in only half of participants, so continuing research is needed for a drug for those who do not respond to mitapivat.

While medical, surgical and radiation oncology have all been accepted in the medical community as effective cancer treatments, interventional oncology has begun to pick up steam as a potential alternative treatment with fewer side effects. Surgery, radiation, chemotherapy, and other traditional cancer therapies have an array of complications and side effects, including pain and risk of death. Using imaging and a catheter-based approach to cancer treatment, interventional oncology seeks to maximize the effectiveness of the treatment without disrupting the remainder of the body.

Interventional oncology actually finds its roots in interventional radiography, which is a subspecialty of radiology that uses imaging coupled with interventional procedures to diagnose and treat diseases. One of the goals of interventional radiography is to use the least invasive method possible to treat a disease, and interventional oncology is guided by the same overarching principle.

One of the most valuable assets that interventional oncology can offer is its ability to aid in both cancer therapy and symptom palliation. Interventional oncology can be used to deliver cancer therapeutic agents directly to a tumor, and can provide the imaging necessary for precise treatment. Interventional oncology can also treat pain through neurolysis, ablation, and bone augmentation. According to Yale Medicine, interventional oncology can be used to treat liver, colorectal, lung, bone/soft tissue, kidney, and metastatic cancers.

The clear advantage to interventional oncology is its ability to treat tumors or symptoms as
effectively as traditional cancer therapies, but without the organ damage, side effects and complications of a traditional cancer treatment plan. As interventional oncology continues to gain authority in the rapidly evolving oncology space, there is potential for this minimally-invasive treatment method to become the future of fighting cancer.

Researchers at the Dana-Farber Cancer Institute and other cancer research institutions have
begun developing a new blood test that is capable of screening for various types of cancer with high rates of accuracy. Investigators reported their results at the European Society for Medical Oncology (ESMO) 2019 Congress in September.

The test was created by GRAIL, Inc and uses a sequencing technology to probe the DNA for
chemical tags, called methylation, that determine if a gene is active or inactive. The test looks for DNA that cancer cells have shed into the bloodstream after they die. This is different to “liquid biopsies” which detect genetic mutations or other cancer-related changes in the DNA. The new test focuses on DNA modifications in methyl groups, which are chemical units that can be attached to DNA and control which genes are turned on or off. When methylation patterns are abnormal, it’s more likely that cancer in present.

In the study, investigators analyzed DNA that had once been inside cells but had since entered the bloodstream. In the trial, the test was used on approximately 3,600 blood samples from healthy patients and patients diagnosed with cancer. The samples came from patients with more than 20 types of cancer including colorectal, esophageal, gallbladder, lung, ovarian and pancreatic. The test was able to detect a cancer signal from blood samples that came from cancer patients and also identified where the cancer originated in the body.

The trial results were 99.4% correct, meaning the results incorrectly found that cancer was
present less than 1% of the time. Investigators pre-specified a set of cancers with high mortality rates and found that the test was also able to correctly identify these cancers. The test was better able to identify the cancers at later stages with its ability to detect cancer as follows: 32% of stage I cancers, 76% of stage II cancers, 85% of stage III cancers and 93% of stage IV cancers. The test was also able to return a result regarding the tissue of origin for 97% of the samples and correctly identified the location in 89% of cases.

While further development of the test is needed to improve its ability to detect early-stage
cancers, most cancer patients whose cancer is caught at an earlier stage have augmented
chances of long-term survival.

A group of scientists from the Dana-Farber Cancer Institute, Massachusetts General Hospital, the Broad Institute of MIT and Harvard and the Ludwig Center at Harvard Medical School studied drug-resistant gastrointestinal stromal tumors (GISTs) to increase their understanding of what causes drug resistance in these tumors. Currently, most GISTs — a type of soft-tissue cancer — are caused by gene mutations that can be targeted with drugs, however, 10% to 20% of GISTs aren’t treatable with current medications.

In the study, investigators showed that changes in how genes are read by tumor cells, but aren’t caused by genetic mutations, can still lead to the development of GIST. Their findings have also indicated further areas of study that could make it possible to stop the development of tumors and treat these drug-resistant GISTs.

In order for a person’s DNA to fit inside their cells, it must wrap itself into loops with points called insulators. Researchers found that one of the insulators that prevents a cancer-causing gene known as FGF4 (fibroblast growth factor 4) is important to understanding drug-resistant GISTs. Another part of DNA has a switch that turns the FGF4 gene on and off. In healthy cells, FGF4 and the on/off switch are on separate loops. But in some forms of GIST, the insulator doesn’t work properly, allowing the loops to merge and turn on the cancer-causing FGF4 gene.

In this study, researchers worked with a form of GIST that had lost the function of the SDH enzyme complex, a key part in creating energy in a cell. These tumors also had an increased rate of DNA methylation, a process that adds chemical “tags” to DNA. The team found that too much DNA methylation destroys insulators in cells, leading to contact between on-switches and oncogenes, including the FGF4 gene and the KIT gene. The KIT gene is usually active in other forms of GIST.

To test their findings, investigators transplanted a human GIST into a mouse and showed that the model maintained the epigenetics of the parent tumor, including increased rates of DNA methylation and defective insulators. They also showed that tumor growth could be suppressed with fibroblast growth factor receptor FGF receptor inhibitors, both alone and with enzyme-inhibiting targeted therapy.

While targeted therapies can help SDH-deficient GIST patients, they typically become resistant to standard targeted therapies quickly. Researchers hope that these findings can open avenues for testing new therapies or repurposing old ones.

The Centers for Disease Control (CDC) and state health departments are currently investigating hundreds of cases of vaping-related illnesses across the country. Vaping has been linked to at least 18 deaths, but the investigations have yet to pinpoint a single ingredient or product as the cause of the illnesses. In addition to the health risks posed by inhaling the vapor, e-cigarette and vape device batteries have been reported to catch fire and cause severe injuries and death. 

E-cigarettes refer to a group of products that users insert a cartridge into. The cartridge contains liquid nicotine, which when heated, creates a vapor that users inhale. Millions of Americans reportedly use e-cigarettes, and in 2018 more than 3.6 million U.S. middle and high school students reported that they had used e-cigarettes in the past 30 days, according to the CDC. 

In August, the Washington Post reported that state and federal health officials were investigating approximately 100 cases of lung illnesses that they believed were linked to vaping and e-cigarette use. Gregory Conley, the president of the American Vaping Association, believes that these illnesses are linked to vaping “home brews” or “street vapes” that contain THC or illegal drugs, rather than the nicotine found in commercially available e-cigarettes. 

Patients who have been treated for these diseases initially presented with symptoms that appeared manageable and were consistent with viral infections or pneumonia, such as shortness of breath, coughing, and fever. However, they would deteriorate despite treatment with antibiotics and oxygen. Some went into respiratory failure and required ventilators. On August 23, Illinois officials reported the first vaping related death in the United States. 

While most people believe that e-cigarettes are safer than smoking traditional cigarettes, they still pose health risks. Although there are fewer chemicals and toxic substances present in e-cigarettes, they contain nicotine, a highly addictive substance. Additionally, users have been known to use the products to smoke “home brews,” which may contain other harmful ingredients. 

Due to the recent emergence of e-cigarettes, there is little research available on the long-term effects of using the devices. But, in light of recent cases, several states have issued health warnings about the devices, as well as temporary bans on the use of flavored vapes, and Massachusetts has issued a four-month ban on the sale of vaping products. 

Glioblastomas are the most common type of brain tumors in adults. They’re difficult to treat due to their location, making them one of the deadliest cancers. The tumors are aggressive, forming new blood vessels and growing rapidly and they can also use connection fibers to spread to the other side of the brain. Treating glioblastomas is difficult, as surgery can be impossible depending on the location within the brain and few drugs can cross the blood-brain barrier to treat the tumors. 

Recently, scientists at Cedars-Sinai in Los Angeles created a treatment by combining an immuno-oncology drug and a polymer-based delivery system that is capable of crossing the blood-brain barrier. In the study, researchers tested the drug combination in mice with gliblastomas. The study’s results, published in Nature Communications, showed that the treatment, called nano-immunotherapy, was able to cross the blood-brain barrier and stopped the tumor cells from multiplying. The polymer delivered two immune checkpoint inhibitors, blocking either CTLA-4 or PD-1. When injected into the mice’s bloodstream, the drugs were able to cross into the tumor cells and treat them, but didn’t affect health brain tissue. 

Past research has shown that brain tumors are able to suppress immune attacks with macrophages and T regulatory cells (Tregs). The researchers at Cedars-Sinai found that after they treated the mice with nano-immunotherapy, the checkpoint inhibitors blocked Tregs and macrophages, allowing the tumor-killing cells to treat the tumors. 

Additional preclinical trials are needed before the nano-immunotherapy is ready to be tested on humans, but Cedars-Sinai’s Julia Ljubimova, lead author of the study, is optimistic about the results. 

“The horizon for treatment of brain cancer is getting clearer,” she said. “We hope that by delivering multifunctional new-generation drugs through the blood-brain barrier, we can explore new therapies for many neurological conditions.”