Chemical biologists create small molecules to boost discoveries or prototype novel therapies
By Eric Bender
Biomedicine always comes down to biochemistry – the exact chemical interplay between the dizzying number of molecules that drive health or disease. In every cancer research center, biochemists study these interactions, develop chemical tools, and collaborate with molecular biologists, genomicists, and other experts in biomedical science.
Within this vast field, chemical biologists focus primarily on designing and synthesizing small molecules for research and treatment. Back in 2006, Dana-Farber launched a bold experiment to accelerate this work: It hired three chemists with ambitious goals and gave them access to resources not usually found in academia.
One hope for the budding Chemical Biology program was that the chemists, in partnership with Dana- Farber physician-scientists, would be able to unlock some of the mysteries that drive cancer.
"A good chemical probe can do a lot for the basic biological understanding of a process, and it's often very complementary to genetic tools," explains Program Director Milka Kostic, PhD. "In genetic research, you usually remove the entire gene. With a chemical compound, you inhibit the activity of the protein, or remove the protein rather than the gene. So that offers you very complementary ways of asking about the function of a protein."
The experiment proved a wild success. By 2015, the first three investigators had published more than 300 papers, filed more than 250 patents, formed eight startup firms, and, most importantly, made major contributions to the creation of six drugs in clinical trials. Two of the drugs, ceritinib and osimertinib, were approved by the Food and Drug Administration (FDA) in 2014 and 2015 for treating non-small cell lung cancer.
Today, the Institute's Chemical Biology program hosts nine principal investigators and more than 100 researchers. Its headquarters, in state-of-the-art facilities at Dana-Farber's Longwood campus, brings together Institute chemists, structural biologists, translational research experts, and other experts under one roof.
Survivorship: DAY ONE
The 'Right Track' to Navigate the Cancer Experience
July 9, 2018
Five leading cancer organizations came together to establish four steps that patients of all malignancies can turn to as they navigate their experience.
“You have cancer.” Those words are often followed by an overload of oncology terms: immunotherapy, precision medicine, genomic testing, clinical trials, progression-free survival, overall survival. It’s an ever-growing list.
But what if there was a roadmap to guide patients before they begin to feel overwhelmed? Five leading cancer advocacy organizations — the Multiple Myeloma Research Foundation (MMRF), LUNGevity Foundation, the Metastatic Breast Cancer Alliance, the Pancreatic Cancer Action Network and the Prostate Cancer Foundation — have come to a consensus on four steps that patients of all malignancies can turn to as they navigate their experience.
First, patients need to find the right team. That means locating the best experts and centers with extensive experience in treating their specific cancer. Next, they should ensure they receive the right tests, meaning the right information and a precise diagnosis. The right team and tests can then lead to proper treatment, which will include a plan and potentially identify clinical trials. Finally, patients should share their data throughout their journey. This step can potentially help not only themselves, but others with the same type of cancer.
A recent study published in The Cancer Journal evaluated where gaps in knowledge exist. It was conducted by the Harvard Business School Kraft Precision Medicine Accelerator, a multidisciplinary initiative focused on four integrated workstreams to advance precision medicine. The five cancer organizations are working as part of the Accelerator’s Direct to Patient workstream.
“What we found is there is an incredible opportunity to help patients get on the right track with tips on how they can research physicians and arm them with the right information to be proactive and informed,” Lori Marcus, who chairs the Direct-To-Patient workstream of the Kraft Precision Medicine Accelerator and has held C-level roles with multiple consumer companies including PepsiCo and Keurig Green Mountain Inc., told CURE in an interview.
The study included patients with pancreatic (108 patients), multiple myeloma (86 patients), metastatic breast (86 patients), lung (56 patients) and prostate (50 patients) cancers. They were all residents of the United States, aged 25 years or older and recruited through email or social media invitation. Patients reported being somewhat knowledgeable of their disease and having some input in treatment decisions.
They were asked to complete an online survey to demonstrate awareness of and barriers to making important medical care decisions. Questions pertained to information such as how they found their physician, or if they were familiar with the term precision medicine and if they had done tissue banking.
“We want to make sure that we are reaching every patient so that they and their doctor have the most cutting-edge, precision-based information to have optimized care,” Anne Quinn Young, MPH, senior vice president of Marketing and Communications at the MMRF and co-author of the study, said.
Upon examining the patient-reported survey, the authors determined that the majority (61 to 76 percent) of patients were referred to their treating physician rather than choosing one themselves. Only 24 to 29 percent of patients among the five tumor types selected their physician.
The authors also discovered that only 36 to 52 percent of patients have ever heard of precision medicine. Genomic testing was not widely known either, with 3 to 38 percent of patients reporting they were very familiar with it. The rate of genomic testing was highest in the lung cancer group and lowest in the prostate cancer group. Among the patients who did not have genomic testing, most (47 to 81 percent) revealed that it wasn’t offered.
In addition to genomic testing, tissue banking has also become increasingly important in the research area of cancer. It can be used to help develop new drug targets and discover new biomarkers. However, only 22 to 28 percent of patients had banked tissue samples. The majority doing so prior to starting therapy.
“Part of what these trusted third-party foundations do is they can help navigate people, whether it’s through their websites or call centers,” Marcus said. “They can help them find their way to a National Cancer Institute-designated center, understand the importance of a second opinion and provide the questions to ask to determine if a doctor sees a lot of different patients with their type of cancer.”
Clinical trial enrollment was also low (less than 15 percent) – and there may be good explanation for this statistic: Patients reported that they feared they would receive a placebo, which is a common misperception. “People don’t realize that they will at least minimally get the standard of care,” Marcus said.
The survey results also showed that there is a lack of physician recommendation for clinical trials. “This goes back to having the right team,” Quinn Young said. “Because even if you’re being seen by an amazing center you can still get a referral to participate in a clinical trial somewhere else, you’re not bound to stay at that one center.”
An exciting finding of the study is that nearly all (86 to 100 percent) patients said that they were willing to share their data to accelerate cancer research. Patients can do so in a variety of ways: Letting organizations know that you’re out there and willing to share, participating in surveys or becoming part of a patient registry.
“If I could get patients to go from a passive perspective … to understand that they can play an active role to ensure they get the best precision medicine outcomes,” Marcus said. “They don’t have to know all the answers, but arming themselves with a little bit of information, a little bit of research and asking the right questions — especially early on in their process — can improve their own outcomes and outcomes for other people.”
As The Partnership continues to foster relationships with our partners, we would like to highlight the work of the Joe Andruzzi Foundation through their Financial Assistance Program. Grant applicants must submit their application through a healthcare professional, and oftentimes recipients choose to apply with the help of a social worker. One of our new Board Members, Dana D'Alessandro Haseotes, is a Clinical Social Worker who has a long-lasting relationship with JAF by providing assistance with the grant application process. We look forward to continuing our connections with partner organizations in similar ways, to provide the education and resources to those who need it most.
Learning About Pathology
Medically reviewed by Stuart J. Schnitt, MD, and George L. Mutter, MD
July 17, 2019
A pathology report describes the findings in a tissue sample (biopsy or excision), which are always submitted to a pathologist after being removed from a patient. The tissue is sliced very thin and stained on a glass slide for a pathologist to examine under a microscope to determine if there is disease present, and if so, what kind.
“Pathology is the hub around which oncology rotates; it’s the center of patient management,” says Stuart J. Schnitt, MD, a pathologist at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC).
Oftentimes, the terminology of these reports can be difficult for patients to understand. In particular, be cautious about complicated abbreviations you do not understand, as their meaning may change with context. Google searches also often produce erroneous or misleading interpretations.
Your doctor will explain the results of your pathology report to you and can answer any questions you have.
What are the different components of a pathology report?
Patient and specimen identifiers
This information includes the patient’s name, birth date, and other personal information. It also details clinical history, the type of biopsy or procedure, and the type of tissue being analyzed.
Procedures often generate multiple specimens that are submitted together to the pathologist in separate containers. In these cases, a letter or number is assigned to identify these different samples submitted. The individual container labels are carefully recorded, including any specific designation (such as “cervical biopsy at 3 o’clock position”) that allows the pathologist to know where it is from.
“Gross” refers to what is apparent to the naked eye. This section is a detailed description of what the tissue looks like, including the size and appearance of the sample on the outside and cut surface. Abbreviations are especially common in this section; examples include “R” for right and “ESS” for entire specimen submitted. An index, or key, of samples prepared by the pathologist for microscopy is also included.
Procedures that generate multiple specimens are labeled accordingly so the clinician knows where each sample came from. “For example, with a colon biopsy, if only one specimen of several has cancer, the clinician needs to be able to relate that to an anatomical location in the patient,” explains DF/BWCC pathologist George L. Mutter, MD.
In the case of tumors, or localized lesions excised with adjacent tissues attached, visual inspection and measurement to nearest structures — like margins — may be included. These measurements as recorded in the Gross Description are only preliminary, as the pathologist does not yet have the definitive microscopic preparations (slides) required to verify where the actual tumor cells are in the specimen.
The final assessment of tumor extent and margins appears in the Diagnosis section, and may be a bit different from what was suspected grossly.
This is the “take-home message”: the most important section of a pathology report, according to Schnitt. It can be found at the beginning or the end of the report and serves as a concise summary of information from the entire pathology report. It is based on the gross description, microscopic examination, and sometimes special biomarker studies.
It is important to note that each specimen part has its own separate diagnosis. “Read the diagnosis for all parts,” advises Schnitt. “Patients may see in the report that a margin is positive but may not realize that an additional specimen taken from the same margin is negative — which means that the final margin is negative, not positive.”
Reports that include cancer in the specimen will classify the specific tumor type and any additional information, such as tumor distribution (stage), biomarker status, and molecular findings that may be useful in management. Some tumors will be assigned a grade — often numbered from 1 to 3, corresponding to well, moderately, or poorly differentiated — that describes how abnormal the cells look under the microscope. A higher number means the tumor cells are more abnormal.
Results of specialized marker studies are not typically ready at the time the pathology report is initially issued and are often reported separately.
The pathologist will note if the cancer has spread to nearby lymph nodes or organs if those are submitted for examination. If a lymph node or surgical margin contains cancer, it is labeled as “positive,” and if it does not, it is “negative.”
A recent addition to some pathology reports is “synoptic reporting.” This is an additional, standardized summary of cancer type and stage for surgical resection specimens. The content and format structure, including coded abbreviations, is customized to each tumor type by agreement amongst pathologists worldwide.
Mutter advises readers to “be prepared: these are medical records that are complicated, factual, the language and vocabulary may be very unfamiliar.”
Talk to your doctor if you have any questions about your pathology report. “Don’t take your report to the internet: your doctor is the best person to help you interpret your report,” Mutter says.