Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How an Emory Professor would Treat Her Own Advanced Endometrial Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Jane Meisel, MD
Associate Professor of Hematology and Medical Oncology, Winship Cancer Institute at Emory University

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Jane Meisel, MD, how she would handle her own advanced endometrial cancer. Dr. Meisel is Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University in Atlanta, GA.

Curious Dr. George: Please consider a hypothetical scenario in which, as a very busy gynecologic and breast oncologist, you noticed that your menstrual periods had recently become heavier and more prolonged, but you thought little about it. But now you have lost 8 pounds without a change of diet or exercise. You consult your gynecologist who finds a normal pelvic exam but is concerned by possible ascites (fluid buildup in the abdomen). She performs an endometrial biopsy, and after abdominal ultrasound, aspirates 10 ml of clear peritoneal fluid. The endometrial biopsy yields a diagnosis of poorly differentiated adenocarcinoma, and the peritoneal fluid is found to contain malignant cells. How do you proceed?

Jane Meisel, MD: The treatment options for endometrial cancer have evolved significantly since I finished my oncology fellowship in 2015, so while advanced endometrial cancer is never a diagnosis one wants to receive, patients have many more potential treatment options now than they did even five years ago. I stress this to patients in clinic every day, and I would try to remind myself of this fact as well, even though I know it might be hard to think rationally like this in the wake of a difficult diagnosis.

Endometrial cancer, when it metastasizes, is most likely to metastasize locally in the pelvis, to pelvic and para-aortic nodes, the peritoneum, and the lungs. In any situation where metastatic cancer is suspected, a biopsy is key, and there is much my treating physicians and I would be able to learn about the cancer from the biopsy. First, the histology—is it endometrioid, clear cell, or serous? Serous and clear cell are associated with worse overall survival compared to endometrioid cancers, and clear cell cancers tend to be more chemoresistant than other subtypes. If it were endometrioid, we would want to do receptor testing for estrogen and progesterone, as this can help with treatment planning; and if it were serous, we would want to do HER2 testing for the same reasons.

All patients with endometrial cancer should have mismatch repair protein (MMR) or microsatellite instability (MSI) testing to understand options for immunotherapy. Somatic mutation testing is often also done (using a next-generation sequencing panel), but this could be done at a point of progression rather than at initial diagnosis, since the first-line treatment is unlikely to change regardless of NGS results.

Given that I am young and healthy, if I had never been treated for endometrial cancer before (in the early-stage setting) and was felt to be a good surgical candidate based on extent of disease, then surgical cytoreduction would be appropriate, followed by adjuvant chemotherapy. If I were not a surgical candidate or if this were a metastatic recurrence (as opposed to de novo disease), chemotherapy as an initial treatment would be appropriate.

The first-line chemotherapy used for advanced endometrial cancer is almost uniformly carboplatin plus paclitaxel. In a clinical trial known as GOG 209, this combination was compared with a cisplatin triplet-based regimen (cisplatin, doxorubicin and paclitaxel) and it was found to have a similar overall response rate, similar progression-free survival, and similar overall survival, with much lower rates of neuropathy and less overall toxicity.

I always tell my patients with advanced or metastatic cancer that the goals of treatment are to help you live as long as you can and as well as you can—and the “living well” part is very important. So, carboplatin and paclitaxel would likely be my first line of treatment (with trastuzumab if I had serous cancer and were HER2+, given that trastuzumab improves progression-free and overall survival in this situation).

While on carboplatin and paclitaxel (plus or minus trastuzumab), I would monitor with CT chest/abdomen/pelvis every three cycles (or more often if I developed signs of progression while on treatment). There is not a distinct tumor marker defined for endometrial cancer, but in some cases (particularly with high-grade serous endometrial cancer), CA 125 can be elevated at diagnosis, and if that’s the case, can be helpful to follow with each cycle or two to help get a window into the response to treatment.

Upon progression or intolerance of chemotherapy +/- trastuzumab, additional options would have to be considered, and along with that, some of the histologic variables previously discussed. If my tumor were mismatch-repair deficient, had evidence of microsatellite instability, or had a high tumor mutation burden (as assessed via genomic testing), immune checkpoint inhibitors such as pembrolizumab or dostarlimab could be used as single agents. These are very well-tolerated agents when given on their own. Endocrine therapy is also an option, particularly for patients who have hormone-receptor positive, low-grade endometrioid cancer. Otherwise, progression would depend on the treatment-free interval.

If my cancer had not progressed until six months or more after completing my last dose of platinum-based chemotherapy (platinum-sensitive), I could be re-treated with carboplatin and paclitaxel again. If my cancer had come back sooner (platinum-resistant is typically defined as recurrence within six months of last platinum agent), then I would consider pembrolizumab plus the oral VEGF receptor inhibitor lenvatinib, which is effective in patients with advanced endometrial cancer that is not MSI-high or mismatch-repair deficient. This could also be employed after another round of platinum-based chemotherapy, if I were platinum-sensitive initially but after another round of platinum-based chemotherapy, either became intolerant of side effects or treatment resistant.

There are other alternatives as well, such as liposomal doxorubin, bevacizumab, and re-treatment with taxanes. There are also a number of clinical trials that are very exciting; among them, trials looking at additional anti-HER2 targeted agents in patients with HER2+ high-grade serous cancer (such as trastuzumab deruxtecan and tucatinib), and trials evaluating different endocrine therapy options for patients with hormone-sensitive endometrial cancer (CDK 4/6 inhibitors and serum estrogen receptor downregulators are good examples).

Overall, I would try to pace myself, as advanced cancer is a marathon rather than a sprint, and make sure that above all, I felt comfortable with my treatment team and in our shared decision making every step of the way.

Dr. Meisel can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How an Expert Would Manage His Own Advanced Prostate Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Marc B. Garnick, MD
Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Marc B. Garnick, MD, how he would handle his own advanced prostate cancer. Dr. Garnick is the Gorman Brothers Professor of Medicine at Harvard Medical School (HMS) and Beth Israel Deaconess Medical Center in Boston, MA. He is also Editor in Chief of the HMS Annual Report on Prostate Diseases.

Curious Dr. George: Last year, you shared with our readers how you, as an expert, would proceed with handling your own severe back pain and spine lesions.

Let’s revisit that hypothetical scenario with some new developments: Further rapid lab studies demonstrated normal peripheral blood counts and no abnormal serum proteins. The back pain stabilized. Digital rectal exam discovered an enlarged, diffusely firm prostate gland with scattered hard foci. Ten transrectal prostate biopsy cores all contained adenocarcinoma with varying degrees of dedifferentiation, Gleason score of 8, repeat PSA was 25.

How should the pathologist handle the remaining tissues? What procedures should a reference laboratory perform? How would genomic, metabolomic, or proteomics inform next steps? And would imaging be helpful?

Marc B. Garnick, MD: With these new developments, the differential diagnosis has now been narrowed. The likelihood of the bone lesions being related to a plasmacytoma or multiple myeloma, though not completely excluded, are less likely. The lead diagnosis now has been established to be a Gleason score 8 prostate adenocarcinoma, which I presume is a Gleason 4+4. Please recognize that based upon the International Expert Consensus on Prostate Cancer nomenclature, this is now best described as Grade Group 4 (GG 4). Grade Group 1 (GG 1) contains Gleason patterns 3+3; GG 2 contains Gleason patterns 3+4; GG 3 contains Gleason patterns 4+3; GG 4 contains Gleason patterns 4+4; and GG 5 contains Gleason patterns 4+5 or 5+5. If this patient did not have suspected metastases to the bones (and even in the setting of metastatic prostate cancer), the pathology biopsy note should mention the presence of any intraductal component, perineural invasion, or lymphovascular invasion, all of which commonly accompany high-grade Gleason cancers.

Recent recommendations now suggest that genomic profiling of the patient both for germline and somatic mutations be assessed. The importance of BRCA (either germline or somatic) mutation has increased in significance, especially since there are emerging associations of prostate cancer being found in families of women with BRCA mutations. The finding of a BRCA2 mutation is associated with a more aggressive biology and could help inform treatments at some later day with the PARP class of therapeutics of platinum-containing agents, given the increased sensitivity of BRCA + cancers to respond to these therapies.

Additionally, if MSI high is noted during molecular testing of tumor tissue, the patient may at some later time be eligible for treatment with an immune checkpoint inhibitor, such as pembrolizumab.

The above consideration of more precise pathologic assessment is more important in a patient who has a GG 4 or 5, in whom there is no obvious evidence of metastatic disease. In such cases, one is trying to assess a probability of the patient having subclinical metastatic disease or being likely to develop metastatic disease. For the patient with already-established evidence of abnormal foci (in this case, the bone lesions), we in the past would have assessed with an Axumin scan; now, the availability of either Ga or F linked prostate-specific membrane antigen (PSMA) scanning would be indicated, both for diagnostic purposes as well as assessing down-the-line utility of PSMA-specific therapeutic ligands, such as Lutetium 177.

Curious Dr. George: What additional testing and what therapy would you deem to be most appropriate at this point?

Marc B. Garnick, MD: Please recall that this patient (hypothetically me) presented with back pain and multiple bony lytic lesions. Regardless of the etiology of these lesions, identification of any impending spinal cord compression must be assessed. While spinal cord compression is an unusual manifestation of de novo metastatic prostate cancer, it is clinically more common in the setting of treated prostate cancer that has progressed to become castration resistant. I would reassess the anatomic locations of the bone lesions, and then obtain a spinal MRI directed diagnostic evaluation, along with a good neurological examination to inform preemptive radiation or surgical considerations if either impending or actual compression is found.

For treatment of newly diagnosed presumably castration-sensitive metastatic prostate cancer, we now have multiple advances that have been established in this disease setting. First-line ADT (generally with an LHRH agonist or GnRH antagonist) is now supplanted with second-generation agents, such as abiraterone (+ prednisone) or enzalutamide, or other androgen-receptor inhibitor agents, such as apalutamide. ADT + chemotherapy with docetaxel is also appropriate. Given the bone pain and potential neurological issues here, I would select a GnRH antagonist (either degarelix or relugolix) as the preferred therapy.

Dr. Garnick can be reached at

Related links:

How Would an Expert Handle His Own Cancer of Unknown Origin Causing Severe Back Pain?

Harnessing Each Patient’s Data to Help Many More

Cancer Commons Adapts to Remain True to Our Mission

A message from Curious Dr. George:

The goal of Cancer Commons is to help patients find and access their best possible treatments, one patient at a time, while moving the field forward. If you have advanced cancer, let our molecular oncology Scientists provide free, personalized information about your options.


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Harnessing Each Patient’s Data to Help Many More

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Kaumudi Bhawe, PhD
Cancer Commons Scientist

At Cancer Commons, we don’t just help people navigate cancer treatment; we learn from everyone we help. Here, our Curious Dr. George asks Cancer Commons Clinical Scientist Kaumudi Bhawe, PhD, to share how new knowledge can be captured from every patient to help many more.

Curious Dr. George: Cancer Commons has accumulated in-depth data on many hundreds of patients with various cancers. Because of the molecular nature of cancers, many are very complex—even unique. How might these data be best studied and reported to help inform diagnostic and therapeutic decisions for many additional patients, who are in need of information to guide their own journeys in precision oncology?

Dr. Bhawe: We are more than just the sum of our body parts.

We are stories, waiting to be told.

This is especially true for cancer patients who are suddenly put face-to-face with the fear of death. Most of the time, their stories remain untold, and this wealth of information and insights may be lost upon the medical community. Most organizations developing new oncology drugs and preventative screens realize the need for deep “N-of-1” studies—essentially, rigorous analyses of individual patients’ testing and treatment outcomes—the nuances of which can be mined for novel, testable insights. But many organizations are not equipped for employing an N-of-1 approach.

Enter Cancer Commons.

Here at Cancer Commons, we communicate in-depth with each person who contacts us to understand their cancer-care possibilities, considering their own unique cancer context. Since we place high value on such a holistic understanding, we can tailor our recommendations of clinical trials and diagnostic testing possibilities in a truly personalized manner. Most patients come back to us when they are faced with a new decision point in their journey, and as a result, we have longitudinal information on these patients, capturing a specific window of time in their lives. Cancer Commons has been helping patients for over ten years now, so we have accumulated a wealth of such information that can be mined for important insights.

Our patients’ interests always come first, so data de-identification to preserve patient anonymity is a must. Once that is done, there are multiple ways to use patient data in order to better understand the relationships between variables that have been captured in the dataset.

One very powerful way to conduct this kind of analysis is by employing a Bayesian machine-learning approach. I will explain below, but in technical terms, this is a statistical strategy in which current knowledge in the field can be used to construct an initial directed acyclic graphical model of an initial multifactorial hypothesis, which itself is a set of nested, interconnected sub-hypotheses wherein there is an initial 50/50 probability of both the overall hypothesis (model) and any nested sub-hypothesis (relationship between two variables in the model) being true. The beauty of such an approach is that the initial model (termed “prior”) can be tested and modified continually in real time as real-world data is added to the dataset, and as new clinical information is added to the larger body of medical literature. See this presentation by Cancer Commons founder Marty Tenenbaum, PhD, for a deeper understanding of the larger conceptual framework of using Bayesian machine learning and artificial intelligence to beat cancer.

So what does the above paragraph really mean?

Let’s take a realistic but fictional example to understand this better. Suppose our question is: “What is an ovarian cancer patient’s likelihood of benefitting from treatment with a novel KRAS inhibitor?” The factors influencing patient benefit might include: cancer stage, grade, histological subtype, number of prior treatments, type of prior treatments, KRAS mutation type, and tumor mutational burden (TMB) status, among others. Our initial directed acyclic graph model (prior) might state that each of the known factors independently, and with equal weightage, feeds into a binary output called “benefit from trial” with two possible states being “yes” and “no”. We assign an initial 50/50 probability to believing that our proposed “prior” is the best representative model of the situation. We can then feed real-world data into a machine-learning algorithm that tests the model (prior) and proposes a “better fit” model based on the data we have at hand. The “better fit” model becomes the “prior” for the next step, and as new clinical information becomes available—in our fictional example, let’s suppose that the novel KRAS inhibitor in question showed benefit to lung cancer patients with a G12D mutation—it can also be accounted for. The above process is thus carried out iteratively, and has the potential to generate novel testable hypothesis-generating insights, such as the following fictional example: “KRAS G12D mutations are associated with low TMB status in some third-line platinum-resistant high-grade serous ovarian cancer patient tumors, and our historic-data-based model predicts these patients as having a higher probability of experiencing greater than one year of progression-free-survival from the novel KRAS inhibitor in question as compared to patients with any other KRAS mutations or TMB status.”

In order for researchers to use computers to carry out the above sort of modeling, data from structured and unstructured sources must be parsed, tabulated, and processed before it can be used as input. But it is important to remember that the above fictional scenario also describes an analytical process that has been used for centuries by practicing physicians and caregivers.

At Cancer Commons, we are a dedicated team of professionals helping each patient navigate next-step possibilities in real time, while curating our collective learning, so as to help future patients navigate their own experiences with precision oncology.

Dr. Bhawe can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Plain Language Summaries Improve Access to Medical Research

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Chris Winchester, DPhil
Chief Executive Officer, Oxford PharmaGenesis

Adeline Rosenberg, MSc
Senior Medical Writer, Oxford PharmaGenesis

Cancer Commons helps people make sense of the latest research on treatments for their distinct type of cancer. Meanwhile, a growing number of research papers now include a plain language summary (PLS)—an overview of the paper written for anybody to understand. Here, our Curious Dr. George discusses plain language summaries with Adeline Rosenberg, MSc, Senior Medical Writer at the healthcare communications company Oxford PharmaGenesis, and Chris Winchester, DPhil, Chief Executive Officer at Oxford PharmaGenesis.

Curious Dr. George: Patients and the public are very interested in the results of much clinical research. In the internet age, many medical articles intended for a research or physician audience are available open access. Yet, even structured abstracts may be difficult to understand. Some journals are now including plain language summaries (PLS) written by the authors. Can you tell us about this movement?

Adeline Rosenberg, MSc, and Chris Winchester, DPhil: Open-access publishing has been a pivotal step in the open-science movement, ensuring that peer-reviewed evidence of the highest quality is available to anyone who needs it, anywhere in the world. Research foundations and charities have taken the lead in funding transitions to open access, with pharmaceutical companies following in their wake.

The logical next step is to make sure that peer-reviewed evidence is understandable by all—this is an area in which pharmaceutical companies are leading the way. Article-associated plain language summaries (PLS) are elements of peer-reviewed journal articles written in jargon-free, accessible language for anyone to read—from patients, policymakers, and the public to non-specialist or time-poor researchers and clinicians. By communicating in a way that is understandable by all, PLS provide equity of information and a basis for shared decision making.

PLS are particularly important in cancer care, where the pace of scientific discovery and the expanding range of treatments can be overwhelming. PLS give clinicians, policymakers, patients, and caregivers the tools they need to empower patients and make decisions about patient care together.

As you can imagine, with a practice that’s still evolving, there is a variety of opinions on what works best. Some journals offer different formats of PLS, such as videos and infographics. Increasingly, journals are publishing short, text-based PLS, which can be indexed on directories such as PubMed alongside the abstract (such as in this cancer research paper). PLS need to be discoverable in order to be found and used, and indexing on PubMed is a great way of optimizing this.

Besides format, there are other PLS aspects on which a clear consensus is beginning to emerge. For example, many people involved in scientific publishing believe that PLS should be an integral part of each journal article and included in the peer-review process for reliability and credibility; that PLS development should involve the authors of the journal article for scientific accuracy and consistency with the overall message; and finally, that drafts of PLS should be user-tested with the target audience to help ensure that they are fit for their purpose and meet end-user needs.

Fortunately, many complementing projects are working towards developing consensus on best-practice guidelines. These include the Patient Focused Medicines Development initiative and the International Society for Medical Publication Professionals’ PLS Perspectives Working Group to name a few. Open Pharma (a collaboration facilitated by ourselves and colleagues at Oxford PharmaGenesis) contributed by publishing our recommendations, which were supported by a commentary on the value of standardizing publishing practices. One pharmaceutical company active in oncology, Ipsen, has even introduced a policy to include PLS in all journal articles reporting Ipsen-sponsored research involving human data. This represents a heartening commitment to transparency and trustworthiness.

As PLS grow in popularity, we hope to see more journals encouraging (or even requiring) the inclusion of PLS, more authors producing them, and more readers engaging with and advocating them. You can join the conversation on social media using #PlainLanguageSummaries—we look forward to hearing from you!

Rosenberg can be reached at and Dr. Winchester at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Can Immunotherapy Be Effective for Brain Cancer?

Matt Warner, PhD
Scientist at Cancer Commons

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Immunotherapy has reshaped the cancer treatment landscape. This type of treatment boosts the immune system to fight cancer. However, for people with advanced brain cancer, immunotherapy options remain slim. Here, our Curious Dr. George asks Cancer Commons Scientist Matt Warner, PhD, about the challenges and future potential of immunotherapy for brain cancer.

Curious Dr. George: An accomplished molecular oncologist, you have now helped many brain cancer patients consider their options, both on your own and as part of virtual tumor boards. Immunotherapy has successfully revolutionized the treatment of many potentially lethal cancers. Why has the use of immunotherapy for brain malignancies seemed to lag?

Matt Warner, PhD: There are several reasons why cancers of the central nervous system (CNS) have been more challenging than other cancers to treat with immunotherapies. Despite recent studies demonstrating that the CNS is not as “immune privileged” as we once believed, it is still clear that 1) the unique anatomy of the brain and spinal cord, 2) the role of the blood-brain barrier at controlling which substances and immune cell subtypes can access the CNS, and 3) the limited presence of the lymphatic system within the CNS all decrease the ability of the immune system to patrol and attack cancers within the CNS versus other organs of the body.

Furthermore, CNS cancers often display fewer mutations in comparison to other cancers and therefore lack the immunogenicity to help the immune system identify and distinguish the cancer from the healthy neuronal tissue.

Lastly, as with all other cancers, you then have to compete with the immunosuppressive tumor microenvironment and the knowledge that chronic and excessive neuroinflammation as a result of hyperactivation of the immune system could also be detrimental to a patient. This presents concerns from a quality-of-life standpoint due to the impact of inflammation and swelling on the function of healthy neuronal tissue. It also poses disease management concerns because the immune system’s response to CNS cancer may also impact the survival, proliferation and invasiveness of gliomas.

CNS cancers therefore present some unique challenges for the immunotherapy-based treatments we currently have available in the clinic, highlighting why the clinical development of immunotherapies for these cancers has been less successful.

Despite these setbacks, I still believe immunotherapies will play a significant role in treating CNS cancers in the future. However, in order to be successful, this approach will most likely require novel combinations of immunotherapy-based treatments (for example, immune checkpoint inhibitors, dendritic cell and peptide-based anti-cancer vaccines, oncolytic viral therapies, and cellular therapy) with radiation, chemotherapies, targeted therapies, and/or Optune. Such combinations will no doubt help us move beyond the prior failings of immunotherapies being investigated as single agents, which lack the necessary activity to single-handedly enhance the immune system and treat cancers within the CNS.

Recent research findings provide some hope in this regard. For example, interim analyses from ongoing clinical studies and retrospective analyses from closed trials that investigated immune checkpoint inhibitors in glioma patients demonstrate that these drugs may need to be used around the time that patients are receiving their surgery, radiation therapy, or Optune treatment, and they may need to be targeted to patients with unique tumor mutational profiles. Additionally, more trials are now exploring combinations of immunotherapies and pharmacological agents to (hopefully) modulate the tumor microenvironment and make it more amenable to immunotherapy-based treatments.

Given how little we still understand about the brain and the activity of the immune system within the CNS, I am confident that we will one day celebrate the successes of immunotherapies in the treatment of CNS cancer patients.

Matt can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Cancer Commons Adapts to Remain True to Our Mission

Shelley Frisbie
CFO & COO at Cancer Commons

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

People facing advanced cancer come to Cancer Commons to ensure they have all the information they need to make their best-possible cancer care decisions. Here, Curious Dr. George asks our CFO & COO Shelley Frisbie about recent updates to our organization.

Curious Dr. George: You have been the CFO of Cancer Commons for some time and recently added the COO title and duties to your position. How do you see Cancer Commons as a 501(c)(3) nonprofit organization as we seem to be emerging from the COVID-19 pandemic? I presume its core mission remains the same, but has the organization evolved, and do you anticipate additional changes?

Shelley Frisbie: There is no question that the pandemic profoundly affected nonprofits, because a significant percentage of philanthropic resources had to be redirected to the COVID-19 fight. Although things were lean at Cancer Commons, we learned from our clients what a tremendous need there is for compassionate, personalized support for those facing advanced cancer. The experience led us to commit even more deeply to our mission.

In support of this, we created the Director of Patient Services role and brought on a Patient Navigation Specialist. They serve as the crucial first points of contact, providing care to those who come to us feeling overwhelmed and uncertain. Together they guide clients through registration, assess needs and goals, and begin the process of identifying appropriate diagnostic and treatment options.

Thanks to an updated, more client-focused website—and the personal outreach done by our navigation team—we are seeing an increase in the number of registrations for Cancer Commons services. With philanthropy down, however, we have had to consider new ways of funding to meet the needs of those turning to us.

With this in mind, we launched several low-cost Enhanced Services, designed to provide a continuum of care:

  • Cancer Commons Plus, a subscription service that ensures registered patients stay connected with their Cancer Commons team for as long as needed;
  • Expanded Options & Navigation, to offer clients more detailed discussion and explanation of potential treatments, and assistance with obtaining molecular testing; and
  • Clinical Trials & Expanded Access Assistance, to address a need clients have been sharing for years.

Something that has not changed is Cancer Commons’ commitment to perpetual learning and open knowledge sharing to help current and future patients. We continue to work with our technology partner xCures on the XCELSIOR longitudinal study and are developing other collaborations to help us offer education and resources. Supported by a memorial sponsorship, we recently launched a series of quarterly webinars to provide critically needed information for cancer patients and caregivers—and introduce a whole new audience to our valuable services.

Everyone needs somewhere to turn when they hear those awful words “there’s nothing more to be done for your cancer.” The questions that arise seem endless. Patients and caregivers are looking for answers to be sure they have done everything possible. Cancer Commons helps provide those answers.

The organization has evolved and will continue to do so. In the near future, we will make Cancer Commons’ offerings even more interactive with the addition of chat service, and leverage partnerships with advocacy organizations and biotech companies so that we can offer new options as technology advances. Philanthropy will always be extremely important to sustain our free services, subsidize Enhanced Services for clients with demonstrated need, and to help us serve as many people as possible.

And as always, I invite anyone facing advanced cancer to sign up to receive one-on-one help from our compassionate experts. We are here for you.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Cellular Aging and the Development of Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Kaumudi Bhawe, PhD
Cancer Commons Scientist

Cancer is so often a disease of older people that a whole medical field, “oncogeriatrics,” exists to address the topic. Deeper understanding of the links between cancer and aging could lead to better treatments. Here, our Curious Dr. George asks Cancer Commons Clinical Scientist Kaumudi Bhawe, PhD, about the relationship between cancer and aging processes that occur in individual cells in our bodies—throughout our lives.

Curious Dr. George: As a molecular biologist, you have worked with many forms and elements of cancer cells. Are there any similarities between the processes of cellular aging and the development of cancer?

Dr. Bhawe: Cancer is a disease of aging. According to the National Cancer Institute (NCI), cancer incidence increases dramatically after age 50, with the median age of people diagnosed with cancer in the United States being 66. While chronological age is definitely a cause of cellular aging, it is not the only cause. In fact, the process of cellular aging is known to happen in cells right from the time a human embryo is still developing. What then, exactly, is cellular aging, and what does it have to do with cancer? This is a timely question with the recent publication of a paper in the scientific journal Cancer Discovery entitled “Hallmarks of Cancer: New Dimensions.” This article highlights aging—or “senescent”—cells as one of the newly acknowledged enabling characteristics of all cancers.

Aging cells can be defined by accumulated damage to the macromolecules, such as DNA and proteins, that are important for the cells to maintain themselves, to grow, and to divide. Certain molecules in a cell, are involved in a mechanism that surveys and repairs DNA damage each time the cell undergoes division. If there is more damage than can be repaired, an aging cell either dies or cannot divide, and goes into what is called irreversible cell-cycle arrest. The above-mentioned mechanism ensures that cells with faulty macromolecules are not increasing in number, and in this sense, it is a disease-preventing mechanism. For a very detailed overview of the DNA-damage-response mechanism and its relevance to cancer, you can read this scientific review article that was published last year.

However, once an aging cell enters irreversible cell-cycle arrest, it can stay alive for quite some time; up to months, as demonstrated by lab-based research. Not only can it stay alive, it can also evolve based on the cues it is receiving from its environment, and importantly, it can alter the very environment it finds itself in. It has been discovered that such senescent cells have an abnormal metabolism and secrete hundreds of different signaling molecules including proteins and lipids. Readers interested in learning more about this exciting field of study can start with this article from the scientific journal Communications Biology and this video from the news site Technology Networks.

Some of the ways in which cells can be induced to undergo aging/senescence include the slow natural aging caused by going through multiple cell-cycles, leading to telomere shortening, exposure to toxic chemicals (including chemotherapy) and radiation, exposure to reactive oxygen species (ROS), and activation of cancer-causing genes (oncogenes). So, you can see that as a cancerous tumor is forming, or even during treatment, senescence mechanisms are at work in at least some of the cancer cells as well as some of the non-cancerous surrounding (stromal) cells, such as fibroblasts, blood-vessel-forming cells, and immune cells.

Three key common features shared between aging cells and cancer-developing cells are:

1) accumulation of DNA defects

2) altered metabolic activity, and

3) an increase in secretion of environment-modulating molecules.

The current challenge lies in discovering and cataloging the specific details of each of these three features in order to identify true molecular similarities, differences, antagonism, and cooperation between the processes of aging and cancer. The NCI funds initiatives for cancer and aging research at premier institutes across the U.S. in the hopes of addressing this challenge and developing new, better strategies for cancer prevention and treatment.

Dr. Bhawe can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

More Information from Less Tissue: Strata Oncology Excels

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Scott A. Tomlins, MD, PhD
Co-founder & Chief Medical Officer, Strata Oncology

Laura E. Lamb, PhD
Director of Translational Medicine, Strata Oncology


For a growing number of advanced cancer patients, molecular testing of tumor tissue is an essential step in identifying their best options for treatment. Strata Oncology is one company offering this kind of test. Here, our Curious Dr. George asks two of its leaders what sets Strata apart.

Curious Dr. George: No loop is stronger than its weakest link. In the “brain-to-brain” concept of laboratory testing for precision oncology, tumor specimen selection, collection, preservation, transportation, and processing are among the most important factors. What characteristics of your company’s approach to molecular diagnostics may be particularly advantageous for physicians to use to best guide cancer diagnosis and treatment?

Scott A. Tomlins, MD, PhD—Co-founder & Chief Medical Officer, Strata Oncology, and Laura E. Lamb, PhD—Director of Translational Medicine, Strata Oncology: Thank you for the opportunity to discuss this important topic. Strata Oncology’s mission is to accelerate the impact of precision medicine for patients with cancer by providing advanced molecular tests coupled to compelling clinical trials. To achieve this, we have carefully considered the brain-to-brain loop as it applies to clinical diagnostics. We are continuously innovating to ensure that all the steps involved in comprehensive molecular testing are optimized, standardized, and intelligently designed to improve benefit to the patient, while also working to reduce testing barriers to physicians and patients by partnering with healthcare systems and integrating Strata testing, education, and clinical trials system-wide.

All molecular testing at Strata is performed in a high-throughput, CAP-accredited and CLIA-certified laboratory, with numerous and redundant quality checks, controls, and standards in place. For example, all histology samples and molecular tests are reviewed and signed out by a single pathologist, which reduces variability, particularly for samples submitted as carcinoma of unknown primary. The latest clinical and molecular data is also reviewed by the lab director to ensure the most relevant information is used to guide downstream therapeutic decision-making. Our commercially-available test, StrataNGS®, has been clinically and analytically validated to assesses DNA and RNA in solid tumors. Importantly, as StrataNGS® sample requirements are some of the lowest in the industry (³2mm2), Strata has over a 99% success rate for patient samples passing all sample input requirements, resulting in over 60,000 tumor samples being tested.

StrataNGS® has been optimized for small tumor tissue samples and fills a critical unmet need. Unfortunately, as many as one out of every two patients with advanced cancer have insufficient tissue for other leading molecular tests. StrataNGS® requires 1/10th the tissue of other tests, which provides more patients the opportunity to benefit. By design, the StrataNGS® testing approach is modular: if the sample meets the overall sample requirements, the DNA, RNA, and tumor mutational burden are tested on three separate panels, which allows for the detected biomarkers to be reported from all or some of the panels, depending on whether the panel-specific quality control metrics had been met. Consequently, 94% of all samples tested by Strata will provide an informative result. Patients whose samples cannot be tested by Strata will not be charged for the test.

To simplify clinical reporting, StrataNGS®uses data-driven and clinical insights to provide an easy-to-follow report for confident clinical decision-making. The report summarizes matches to FDA-approved and guideline-recommended therapeutic regimens for all guideline-recommended genes, as well as matches to investigational therapies through clinical trials, including those available through Strata Oncology’s clinical trial partners, or the company’s own sponsored clinical trials Strata PATH and SENTINEL.

Strata Oncology builds processes within the company and through our partnerships with healthcare systems and biopharma companies to reduce testing hurdles for oncologists and their patients. In doing so, we aim to continue to bring the latest innovations in genomics, transcriptomics, and precision medicine to all patients with cancer, while collaborating with our partners to generate and test new biomarker-guided treatment hypotheses.

Dr. Tomlins can be reached at, and Dr. Lamb at

Meet Deb Christensen, Nurse Navigator for People Facing Advanced Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Deb Christensen, MSN, APRN, AOCNS, OCN
Director of Patient Services at Cancer Commons

For people with advanced cancer, making sense of the complexities of cancer treatment can be truly daunting. Enter the oncology nurse navigator (ONN), a nurse with specialized training to help patients overcome any barriers they may face in accessing high-quality cancer care. At Cancer Commons, our Director of Patient Services Deb Christensen, MSN, APRN, AOCNS, OCN, applies her ONN training to ensure that every patient receives the guidance they need. Here, our Curious Dr. George asks her about her work.

Curious Dr. George: You are in charge of patient services at Cancer Commons. How would you describe how you use your ONN skills every day to assist patients with advanced cancer who seek help at Cancer Commons?

Deb Christensen, MSN, APRN, AOCNS, OCN: My first real exposure to oncology was as a nurse navigator in a large healthcare organization. Care coordination is one of the main roles of the ONN. Networking and forming partnerships with other departments and physician offices was key to successfully helping people navigate the complex landscape of oncology care. I had the opportunity to participate on a committee of nurses who updated the Oncology Nursing Association Nurse Navigator Competencies in 2017 and was coeditor of Oncology Nurse Navigation: Delivering Patient-Centered Care Across the Continuum (second edition).

These experiences allowed me to share my passion for the role of the ONN and grow in the profession. After working as an ONN, and then serving as the system lead for the navigation program, I retired from the organization and joined Cancer Commons as a nurse navigator.

I am peoples’ first point of contact at Cancer Commons. I assist people through the registration process and then contact them to learn more about their cancer history and assess their needs, goals, and expectations. An essential ONN skill that I use consistently is the ability to communicate in a way people can understand and follow. Our patient navigation specialist, Lauren Levine, and I assist the patients and their families with retrieving medical records, collaborating with our Scientists, and checking in at key points in the cancer journey. Our goal is to make the entire process personalized and as simple as possible. The entire Cancer Commons team collaborates to help clients create a plan to discuss with their local oncology team. This action plan is complimentary, informed by the latest scientific research, and curated by PhD scientists.

My new role as Director of Patient Services evolved out of the Cancer Commons team’s desire to provide a more personalized experience to clients and offer new services. Our team helps clients understand their treatment options and take potential next steps. Additional services being implemented include a Cancer Commons Plus subscription for ongoing follow up and communication with the science team, clinical trial enrollment assistance, and other assistance offered by the hour. The ability to put clients first by providing non-biased treatment options and timely compassionate care is at the heart of everything we do at Cancer Commons.

Deb can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Cardiometabolic Medications That Inhibit mTOR Might Help Prevent or Treat Cancer

Curious Dr. George Cancer Commons Contributing Editor George Lundberg, MD, is the face and curator of this invitation-only column

William H. Bestermann Jr, MD Senior Clinical Advisor at Congruity Health

Many people believe that cancer is a metabolic disease. A biological process known as the mTOR pathway controls cellular metabolism by way of central signaling, and it is involved in tumor growth. Here, our Curious Dr. George asks William H. Bestermann Jr, MD, an internal medicine doctor, how medications that target the protein mTOR and its associated pathway could prevent or treat cancer. Dr. Bestermann is Senior Clinical Advisor at Congruity Health.

Curious Dr. George: What drugs that are currently approved for use by the U.S. Food and Drug Administration (FDA) inhibit mTOR and might be worthy of testing for potential off-label use for cancer prevention or therapy?

William H. Bestermann Jr, MD: A search including the terms mTOR and cancer in PubMed brings up 125,000 articles on the subject. Aberrant mTOR activation and signaling play a central role in many malignancies. Mutations that persistently activate mTOR are a basis of many familial cancer syndromes.

So, what is mTOR? It is an abbreviation for the mechanistic target of rapamycin, which is a natural compound produced by a fungus. Rapamycin is an antibiotic that is slowly released from the most modern heart artery stents to keep them from blocking with scar tissue and inflammation. It accomplishes that by inhibiting the protein mTOR, a master metabolic genetic switch. The mTOR pathway regulates many metabolic processes. In the fetus and child, it is essential to coordinate food availability with growth. Overeating, excess abdominal fat, and tobacco smoke cause increased oxidant production and growth factor signaling, which activate mTOR to increase arterial thicknessheart size, and the likelihood of cancer. mTOR has a reciprocal relationship with the protein AMPK, another genetic master metabolic switch. When mTOR is switched on, AMPK is switched off. mTOR and AMPK are a final common signaling pathway for genetic signaling that causes heart disease and malignancy. Medications that block oxidant production from that signaling or directly impact the mTOR/AMPK axis inhibit malignant transformation and tumor growth.

Several cardiometabolic medications decrease oxidant production and epidermal growth factor receptor (EGFR) activation to switch off mTOR and switch on AMPK. These include ACE inhibitors like lisinopril, ARBs like losartan, statins, and mineralocorticoid receptors (MR) like spironolactone. Smoking cessation has the same effect. Caloric restriction, intermittent fasting, rapamycin, exercise, and metformin directly inhibit mTOR and activate AMPK. SGLT2 inhibitors directly activate AMPK. These components of optimal medical therapy interfere with the core biology that causes cardiovascular disease and cancer. That is why they have a greater impact on major cardiovascular events and all-cause mortality than their impact on the target risk factor. These interventions don’t merely lower the target risk factor, they interfere with the molecular biology that causes cardiovascular diseases and cancer. They protect cells and organs.

Medications with a structure and function similar to rapamycin are called rapalogs. These are used to treat cancer and prevent organ transplant rejection, and they have potential in several additional conditions. The cardiometabolic medications listed in the previous paragraph do the same thing by directly or indirectly switching off mTOR and activating AMPK. Rapalogs inhibit both mTORC1 and mTORC2. The effect on mTORC1 is beneficial, and inhibiting mTORC2 may have harmful side effects. Like rapalogs, metformin has a beneficial effect in cancer prevention and treatment, which it produces by directly and specifically inhibiting mTORC1 and activating AMPK. Statins and ACE inhibitors are also associated with decreased cancer incidence. Similarly, high aldosterone levels have been associated with increased cancer risk, and eplerenone blocks those effects in a highly specific manner.

Research to further evaluate cardiometabolic medications for cancer prevention and treatment benefit should be a priority.

Dr. Bestermann can be reached at