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

Using Live Cells from Patients to Find the Right Cancer Drug

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

Clifford A. Reid, PhD
CEO, Travera

Today, many cancer patients benefit from targeted drugs that are matched to the distinct genetic mutations found in their tumors. However, especially in late-stage cancer, this “precision oncology” strategy has not proven to be as transformative as people once hoped. Here, Curious Dr. George asks Clifford A. Reid, PhD, CEO of Travera, how his company is addressing this problem.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved about 270 anti-cancer drugs. The National Comprehensive Cancer Network publishes guidelines for treatment of about 61 major cancer types. There is consensus on 1st– and 2nd-line therapy for most, but great divergence on best 3rd-line treatment. Precision oncology based on population studies not only usually fails but is a false premise. What is Travera doing to convert the promise of effective and efficient targeted drug therapy into reality?

Clifford A. Reid, PhD: The original goal of what we now know as “precision oncology” was to understand the root genetic cause of each cancer, and then design a set of targeted drugs to attack each of these cancer-causing DNA mutations. At the time, this was called “personalized oncology,” and its promise was to deliver “the right drug to the right patient at the right time” based on the DNA mutations in each cancer. Unfortunately, this approach has not worked. While the cancer research community has identified hundreds of cancer-causing DNA mutations, drugs that target these mutations inexplicably don’t work for many patients that have the targeted mutations. To our great disappointment, the promise of personalized oncology is not being realized by these genetically targeted drugs.

A small part of the cancer research community has long recognized that it is simply impossible for the results of a clinical trial to generate personalized therapies for each individual patient. Clinical trials are fundamentally designed to include a population of “similar” patients, and get drugs approved for that population. But we know that cancers are highly heterogeneous, especially in late-stage patients, and that no “one size fits all” result of a clinical trial can address each individual patient’s unique cancer.

That part of the cancer research community has focused on developing tests that directly measure the response of an individual’s live cancer cells to a large set of cancer drugs. This direct-measurement approach not only incorporates everything we know about how cancers and cancer drugs work, but also incorporates everything we don’t know. It simply tries a variety of cancer drugs on each patient’s live cancer cells to find the drug or drug combination that will work for that patient at that moment in time.

While this direct-measurement approach may seem quite obvious, as it works beautifully for selecting the right antibiotics for patients with bacterial infections, it has never really worked in cancer, despite decades of efforts. The fundamental problem is that cancer cells, which are so robust inside a patient, become extremely fragile when removed from the patient, and typically die before most cancer drugs can be tested against them. Efforts to keep the cells alive long enough to test them have backfired: cancer cells forced to stay alive change how they respond to cancer drugs, and no longer behave like the cancer cells inside the patient.

Travera is the first company to develop a test that is fast enough to measure the response of cancer cells to cancer drugs without having to force the cancer cells to stay alive for many days outside the patient. Using a new measurement tool invented at the Massachusetts Institute of Technology (MIT), Travera measures the weight change of individual cancer cells in response to cancer drugs. It turns out that for most cancers and most cancer drugs, if the drug is going to kill the cancer cells in a few days, then it changes the weights of the cancer cells in a few hours, but by an amount too small to be detected prior to the MIT invention. Travera uses this exquisitely sensitive measurement tool to offer its Rapid Therapy Guidance test with 2-day turnaround time and high predictive accuracy. The test is now available for most cancers (including all carcinomas) and for over 100 FDA-approved cancer drugs.

For more information, please visit Travera at

Dr. Reid can be reached at

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

How Would an Expert Manage His Own Advanced Hodgkin Lymphoma?

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

Chief of Oncology, Alameda Health System; Institute for Health Policy, University of California San Francisco

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 oncologist Kevin Knopf, MD, how he would handle his own advanced Hodgkin lymphoma.

Curious Dr. George: Please consider this hypothetical scenario: as a very busy practicing clinical oncologist during the COVID-19 pandemic, you were not paying much attention to your own health when you noticed a weight loss of 7 pounds, a dry cough, and a little fever and sweating at night. Your home COVID-19 antigen tests were negative, but you found some enlarged cervical lymph nodes. Your physician confirmed the lymphadenopathy and palpated an enlarged spleen. Your hematocrit was 39, and WBC 16, 000. CT scan detected both para aortic and mediastinal lymphadenopathy. Biopsy of a cervical node was diagnosed as nodular sclerosing Hodgkin lymphoma. How do you proceed?

Kevin Knopf, MD, MPH: First, which chemotherapy regimen would I pick, given the treatment is with curative intent? Three standard choices: ABVD, BEACOPP, and A-AVD foster intense debate amongst oncologists. A recent Twitter poll by Dr. Aaron Goodman (of the University of California, San Diego) had opinions split evenly between R-CHOP, R-BEACOPP, and A-AVD. The choice has subtle nuances; my feeling is ABVD is probably fine for young patients where the risk of bleomycin pulmonary toxicity can be monitored closely; for myself I would choose A-AVD and monitor carefully for neuropathy.

Where to be treated? Where I live in the East Bay of California’s San Francisco Bay Area, there are centers for the University of California, San Francisco (UCSF) and Stanford, and Dr. Andreadis—a friend—is at UCSF, and Dr. Barbara Galligan, my former resident whom I helped mentor into oncology, are all excellent. By a thin margin I would choose Dr. Rajesh Behl in Berkeley in the East Bay. He is a smart oncologist and I appreciate his dry sense of humor. Getting in and out of his office for treatment would be easy, and it is with the infusion nurses that I would spend 98% of my time.

I am fortunate that my insurance would cover the complete cost and my choice of physicians, but this illustrates an area of oncology I spend a lot of time thinking and writing about: cost effectiveness and health equity. There are broad disparities in cancer care—within the U.S. and worldwide—such that many patients with a curable cancer, such as Hodgkin lymphoma, are not cured.

Pricing for cancer care seems arbitrary and is not really negotiated. In classic economics, one would pick amongst my 5 treatment options based on the lowest cost of care, as the outcome is almost certainly equal. There is a mind-blowing aspect of American health insurance: when Obamacare was enacted, insurance companies’ net profit was capped at 15% of the medical loss ratio, meaning the more my insurance company spends, the more money they can make. My premiums have jumped 15% in 2023. A-AVD is 108-fold more costly than ABVD. Cancer care in the U.S. is virtually “all accelerator, no brake,” and the cost of care keeps rising each year, and health disparities widen.

Sociologist C. Wright Mills quipped “the most important thing you can do in a capitalistic society is choose the right parents.” I chose wisely and ended up with “Cadillac” health insurance. All other industrialized nations have a single-party payer system to pay for care, while U.S. health care delivery is based on a for-profit model. American health care works out well in this particular hypothetical example, but overall, we rank about 50th in the world in terms of healthcare efficiency—tied with Bulgaria.

There are casualties. Half of the U.S. has medical debt, 50% of women with metastatic breast cancer are being pursued by debt collectors, and 42% of newly diagnosed cancer patients will go bankrupt within 3 years of diagnosis. We have a tragic and widening cancer disparity gap in the U.S. and a large care gap between first-world nations and low- and middle-income countries. In many parts of the world, a similar patient would not receive curative chemotherapy. People speak of the American health care “system,” but that would imply a formal interconnected design rather than our Byzantine way of paying for health care. So I might come out of this diagnosis just fine, and not bankrupt, but that was just a simple twist of fate.

Dr. Knopf can be reached at

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

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

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

Bert Vorstman, MD
Urologic surgeon (retired)

Ronald Piana
Freelance science writer, specializing in oncology

In 2020, writer Ronald Piana shared with our readers his own experience of using hydrogen peroxide to quickly eradicate a clinically diagnosed pre-malignant oral leukoplakia—a condition that can develop into oral cancer. Here, Curious Dr. George follows up with him and hears an additional perspective from retired urologic surgeon Bert Vorstman, MD, MS, FAAP, FRACS, FACS.

Curious Dr. George: About 2 years have passed since you shared your story.  Has the lesion reappeared or does it remain “disappeared”?

Ronald Piana: As noted in my 2020 Curious Dr. George post, in 2018 I presented to my dentist with a raised 3-cm lesion on the lateral border of my tongue, where most cases of squamous cell carcinoma (SCC) occur. After treating the lesion with four separate topical applications of high-concentration H2O(hydrogen peroxide), it disappeared. To date, there has been no recurrence, which indicates that direct-contact application of high-concentration H2Ohad sufficient cell-kill penetration to “cure” the premalignant lesion.

Curious Dr. George: Have you learned of any other people who have tried the peroxide treatment for similar lesions? If so, what are the results?

Ronald Piana: Since the publication of the 2020 blog post, I have received several emails from people around the country seeking advice on treating suspicious lesions with high-concentration H2O2. All, except for one, have been oral lesions similar to the one I presented in the original blog post. Every oral lesion was treated successfully, and on follow-up emails 6-months post treatment, there has been no recurrence.

I would like to introduce to you Bert Vorstman, MD, MS, FAAP, FRACS, FACS, a retired urologic surgeon in Coral Springs, Florida, who has offered to share a case history of the exception, which involved squamous cell carcinomas of the face and leg.

Bert Vorstman, MD, MS, FAAP, FRACS, FACS: Some months ago, I happened on the Curious Dr. George blog post about Ronald Piana’s experience with the treatment of a suspicious tongue growth with high-concentrate hydrogen peroxide—a simple over the counter application that cured his precancerous lesion.

As a physician and outdoorsman, I was intrigued by this easy self-treatment as I had been visiting the dermatologist for years to have various squamous cell cancers burnt off with liquid nitrogen, an uncomfortable and costly procedure. Superficial skin cancers and precancers consistently recur, a reason why dermatologists have you coming back for office visits every few months or so for a check and burn, and maybe a biopsy or two for good measure.

I decided to try the treatment and purchased a bottle of food-grade 33 percent H2O2. I used a dropper to soak a Q-tip with H2O2 and applied it to a squamous cell cancer on the right side of my face. After 10 to 15 seconds, I could feel some tingling and mild discomfort. After 30 seconds or so I could see that the area in question had turned a speckled white. The tingling and mild discomfort soon settled. I applied the peroxide morning and evening for 2 to 3 days and stopped. Within a few days there was no sign of the lesion.

In between dermatology visits I noticed the development of another typical skin cancer on my right lower cheek; red, scaly and sensitive. I used the H2Otreatment, and the skin cancer disappeared.  After this success, I became concerned about a small spot on the right side of my nose and one on the outer part of my left lower leg. Both of these areas received the same treatment as I had done to my face. These areas also disappeared. And, three months later when I returned to the dermatologist. I didn’t tell her about the areas I had treated but she could not find any areas of concern. Periodic self-examination and self-treatment with 33 percent H2Owas a lot easier, more convenient, and much less costly than visiting the skin doctor. This process also eliminates the long waiting time to get a referral and convenient appointment, which can also prevent treatment delay and potential disease progression.

Moreover, simple H2Otreatment can obviate the potential for Mohs surgery, an expensive procedure that can result in surgical defect requiring a plastic surgeon to undertake a complex closure to fully reconstruct the surgical site. The self-diagnosis and self-treatment of superficial squamous cell cancers with food strength hydrogen peroxide is easy, convenient and cheap.

Ronald Piana: The cytotoxic potency of H2O2 is well documented; however, its clinical value in cancer treatment has largely remained overlooked. In the report by Mundi, et al, the authors offered several hypotheses about the mechanism of action by which H2Oeradicated squamous cell carcinomas. It is beyond the scope of this post to delve at length into those complex biochemical processes. However, my research of the literature concerning the cytotoxic properties of H2Ohas found a scientifically sound hypothesis based on the cancer cell’s own inherent weakness. Studies have shown that all but one human cancer cell type, a human renal adenocarcinoma, have low levels of catalase, thus, the vast majority of cancer cells lack the biochemical machinery needed to detoxify higher fluxes of H2O2.

More important, lysosomes (aka “suicide bags”) do not contain hydrogen-peroxide-degrading enzymes, such as catalase or glutathione peroxidase. During oxidative stress, large amounts of hydrogen peroxide enter the lysosomal compartment, with the formation of abundant hydroxyl radicals, or highly reactive iron-centered radicals, destabilizing the lysosome to the point of rupture, leading to cell death. In short, H2O2 is a proven Trojan Horse compound that permeates the cancer cell and induces a cascade of suicidal events. This post argues that given its enormous anticancer potential, H2Otherapy deserves further testing so that it can be integrated into appropriate clinical settings.

Ronald Piana can be reached at

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

10 Things I Learned in 10 Years at Cancer Commons That Could Save Your Life

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

Marty Tenenbaum, PhD
Founder of Cancer Commons

After facing his own cancer, Marty Tenenbaum, PhD, founded Cancer Commons to help others dealing with the disease. Here, Curious Dr. George asks him to share what he has learned.

Curious Dr. George: As a well-known survivor of metastatic melanoma, and as the founder of Cancer Commons, you are often sought out by friends and acquaintances who have just been diagnosed with cancer or have been told that their cancer has spread. What do you typically tell them?

Marty Tenenbaum, PhD: In my experience as a patient and as the founder and Chair of Cancer Commons, I have gleaned wisdom that every patient should know to have the best chance of beating the odds.

When I was a patient 25 years ago, much less was known about cancer than is known today, and there were far fewer options for treating it. Today, we know that cancer covers thousands of molecularly distinct diseases, and that hundreds of therapies are available to treat it. What no one knows is the optimal way to treat your cancer. The best treatment likely involves an individualized combination of targeted- and immuno-therapies. There are far more rational regimens than can be tested in clinical trials. I founded Cancer Commons to help patients navigate this maze and achieve the best possible outcome.

Here’s my advice:

  1. Patients who take charge of their care fare better. No one else has the time or motivation that you do to dig into your case. Keep your eyes open. A clinical trial you hear about, or something subtle you see can make a life-or-death difference. My life was saved by a clinical trial someone told me about, involving a treatment that ultimately failed clinical testing. But I was fortunate to be an exceptional responder, and the treatment saved my life. But maybe that wasn’t an accident. Early on, I noticed that I was getting a much stronger reaction to a vaccine when it was administered by a particular nurse. Thereafter, I demanded that nurse, and sometimes stayed overnight if she was unavailable that day. Years later, I asked the principal investigator whether he had ever re-analyzed the trial data according to which nurse was administering the treatment. He answered, “why would I do that?” I responded, “because your trial might have been successful.”
  2. Your first and most important decision is choosing the right doctor. The difference between the best and worst doctors can be measured in years of survival. Generally speaking, major academic cancer centers deliver much better outcomes for complicated cases than community oncology centers. Their physicians specialize in particular cancers so it is easier for them to stay up to date. They also participate in clinical research and hence can offer access to clinical trials. There are exceptions. My own life was saved by an extraordinary physician-scientist named Don Morton, MD, who chose to practice in a community setting because he felt that gave him more freedom to try innovative things beyond the standard of care. Major cancer centers expect their physicians to adhere to evidence-based guidelines, which raises the average outcome but holds back top performers like Dr. Morton.

  3. Get your tumor tested for genetic mutations. Knowing the molecular drivers of your cancer allows your doctor to precisely target them using a cocktail of drugs that attack specific types of cancer cells. Such targeted therapies can deliver better results, with fewer side effects than traditional chemotherapies, which target all rapidly replicating cells, including those comprising your hair and intestinal linings. A minority of patients get this testing. Demand it, and don’t be afraid to request that your tumor be sent out to a world-class lab. Cancer Commons can guide you to appropriate providers.
  4. Avoid trial and error. When possible, have your care team test potential therapies for efficacy in a lab or on a computer before giving them to you. This might involve, for example, applying a proposed therapy to fresh tumor tissue from a biopsy, or to an organoid or cell line grown from fresh tissue, or testing a proposed therapy virtually on a computer model of your tumor. You can only try a handful of treatments over the course of your disease. Make sure they’re the best. Then monitor your actual response to therapy and be prepared to pivot if necessary.
  5. If you’re fortunate enough to drive your cancer into remission, stay vigilant. Regular scans and blood tests are essential to detect and respond in a timely fashion to a recurrence. Getting PET/CT scans every six months saved my life; a metastasis was detected five and half years after I thought I was cured. Very sensitive blood tests can now detect minimal residual disease 10 to 100 times smaller than what can be seen on a scan.
  6. Many patients, upon achieving remission, celebrate by suspending treatment, hoping their cancer will not return. But battling cancer is not a boxing match, where you knock your opponent down and the ref sends you to your corner until they get up. It’s a knife fight. When your opponent goes down, step on their throat and finish them off. Remission is the time to try immunotherapies that can mop up remaining lethal cells.
  7. Many oncologists dismiss surgery as an option for metastatic cancer. You shouldn’t. While surgery is not indicated for widely disseminated disease, it can control isolated metastases and reset the clock to give systemic therapies a chance. I speak from first-hand experience.
  8. Most tumors are not homogeneous. They are evolutionary ecosystems of molecularly distinct sub-populations competing for survival. They have different rates of replication, evolutionary fitness, sensitivity to a chemotherapy, and different potential to kill you. It’s important to understand these dynamics in choosing a therapeutic regimen—which therapies, in what order, dosing, and timing—because the last thing you want to do is to wipe out all the easily killed cells that are holding the lethal cells in check.
  9. Don’t let dire survival statistics intimidate you. By definition, half of all patients exceed the median survival, and there’s a long tail that can stretch many years. Following my advice will help you beat the odds. Case in point, me.
  10. The best way to cure cancer is to catch it early. A new generation of molecular screening tests is making that possible. If you test positive, Cancer Commons will help you identify and access the best treatments.

While Cancer Commons is committed to helping everybody regardless of their means, the reality is that some treatments may only be available to those who can pay for them out of pocket. If you are so fortunate, be advised that there are options available far beyond what can be offered to most patients, ranging from experimental, personalized vaccines to engaging a scientific team specifically to research your cancer and how most effectively to treat it. Cancer Commons can help you access these options, and what we learn can help many other patients.

Dr. Tenenbaum can be reached at

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

A Powerful Knowledge Base for Precision Oncology

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

Hongxin Zhang
Lead Software Engineer OncoKB, Center for Molecular Oncology Memorial Sloan Kettering Cancer Center

Genetic mutations found in a tumor can be important clues to the patient’s best treatment options. Memorial Sloan Kettering Cancer Center (MSK) in New York has developed a product called OncoKB, which enables anyone to access and navigate key clinical information about the various genetic abnormalities that may be found in tumors. Here, Curious Dr. George asks MSK Lead Software Engineer Hongxin Zhang about this tool.

Curious Dr. George: At the 2022 Precision Medicine World Conference in Santa Clara, CA, you outlined how OncoKB can be of great value for investigators, drug developers, regulators, educators, clinical oncologists, and patients. Offered through a 501(c)(3) organization, how can OncoKB help other 501(c)(3) charities access focused information and options for people with advanced cancer?

Hongxin Zhang: Precision oncology is defined as using molecular profiles to identify clinically actionable driver alterations in patient tumor samples. It has become the standard of care for many cancer types, and there are many steps between having a patient consent to tumor sequencing and having a clinical oncologist make a decision on the basis of the patient’s tumor molecular results. Interpretation of sequencing results is confounded by the sheer number of alterations that can surface from next-generation sequencing (NGS), but is a critical step in the utility of clinical NGS testing and consequent clinical decision making.

Tumor-specific (or “somatic”) mutations are divided into those that are causal in tumor development, so-called driver mutations, and those that are benign bystander mutations, or “passengers”. Most of the variants detected in a patient tumor sample are passenger mutations. A small subset of driver mutations can serve as predictive biomarkers of response or resistance to targeted therapies, and these mutations are considered clinically actionable.

The challenge for clinicians and researchers is how to reliably identify a clinically actionable variant. Information describing a variant’s biological and oncogenic effect and clinical actionability is buried in various unstructured resources, such as the text of scientific research papers. Therefore, the process for a clinical oncologist or molecular pathologist to accurately and reliably identify actionable mutations and make a timely clinical decision is time-consuming and laborious. Also, new data regarding predictive biomarkers is always emerging, making NGS sequencing-based clinical decisions require the practitioner to be completely up to date on advancements in molecular and clinical oncology.

OncoKB is a precision oncology knowledge base developed at MSK that contains biological and clinical information about genomic alterations in cancer. Alteration- and tumor type-specific therapeutic implications are classified using the OncoKB Levels of Evidence system, which assigns clinical actionability to individual mutational events. Annotations are provided based on sample biomarkers and through high-performance programmable access. This ensures the timely delivery of clinical interpretation.

OncoKB implements multiple steps to ensure content quality. First, all content is curated by oncology medical fellows, translational cancer biology postdoctoral fellows, or graduate students. All scientific and clinical content is supervised and reviewed by the OncoKB PhD-level Scientific Content Management team per the OncoKB standard operating procedure. Second, all clinical evidence must be approved by our Clinical Genomics Annotation Committee, which consists of about 50 clinicians across all disease teams at MSK. Third, we introduced an External Advisory Board (EAB) composed of leaders in the cancer genomics field across major cancer hospitals. The EAB members oversee OncoKB development and mitigate any issues arising from conflicts of interest. Based on this model, OncoKB has been annotating patient results from MSK-IMPACT™, an NGS-based multiple-panel sequencing assay, since 2016, with roughly 12,000 samples annotated yearly.

Initially introduced to the public space in 2016, OncoKB became the first somatic cancer human variant database to be partially recognized by the U.S. Food and Drug Administration (FDA), in October 2021.

Our mission is to make accurate genomic biomarker annotation available to as many users as we can. We believe that an expert-curated resource like ours would benefit the whole oncology community. Institutions frequently lack the tools and expertise required to conduct a thorough analysis of genetic data, especially those located in underrepresented communities. OncoKB is free to use in an academic setting, which includes all research projects in all 501(c)(3) organizations. Additionally, a commercial license can be provided if annotation is used in the report. The cost is determined by report volume, business size, and particular usage. If you are interested, don’t hesitate to get in touch with us.

Zhang can be reached at

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

Cancer Commons Helps Patients Benefit from Clinical Trials

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

Emma Shtivelman, PhD
Cancer Commons Chief Scientist

For many years, people with advanced cancer who turn to Cancer Commons have benefitted from working with Chief Scientist Emma Shtivelman, PhD. Here, she shares three patients’ stories.

Curious Dr. George: You have helped many hundreds of patients with advanced cancer to feel valued, to better understand their disease and their clinical situation, and to explore their options. Will you please share with our readers a few de-identified examples of patients who benefited from your assistance?

Emma Shtivelman, PhD: In my years of work with numerous advanced cancer patients, I have experienced many sad developments—as expected when dealing with advanced cancers—but also some moments of satisfaction with the results of my efforts. Here are a few examples:

Case 1: A 64-year-old woman came to us with triple-negative breast cancer metastatic to her lung and significant thoracic lymphadenopathy. She had been treated with two lines of chemotherapy and stereotactic body radiation therapy (SBRT) to her lung tumors, with poor response. Cancer Commons suggested and facilitated mutational analysis through our partner Tempus, which showed a TP53 mutation and RB1 copy number loss, as well as amplification of several genes, including PD-L1 and PD-L2. PD-L1 protein was, however, negative in immunohistochemistry (IHC) testing.

At this time, a single scientific publication documented a high rate of durable responses to anti-PD-1 drugs in solid tumors that have amplification of PD-L1/L2 (a very rare event), even in the absence of detectable PD-L1 protein. Based on these results, I suggested to the patient that she seek enrollment in a clinical trial known as DART, which offers the immune checkpoint drug nivolumab with or without the drug ipilimumab for rare tumors and includes a patient cohort specifically for people with PD-L1 amplification.

The patient started treatment with nivolumab and had a remarkable response, with resolution of her lung tumors and significant reduction of her lymphadenopathy. Now, more than two years later, she is maintaining this remarkable response with some slightly enlarged mediastinal lymph nodes as the only sign of cancer.

Case 2: I began working with a 58-year-old woman with metastatic endometrial cancer after she had received three lines of chemotherapy, followed by recurrence each time. Next-generation sequencing (NGS) analysis of tumor DNA detected loss of function mutations in ARID1A and ATM, as well as amplification of HER2.

At this time, the U.S. Food and Drug Administration (FDA) had approved the drugs pembrolizumab and lenvatinib as treatment for endometrial cancer, and this was planned as the next line of treatment for her. I suggested she also consider treatment in two trials, with the more preferable one offering the drug ceralasertib (an ATR inhibitor) in combination with trastuzumab deruxtecan (an antibody drug conjugate to HER2 with so-far unsurpassed activity in HER2+ breast cancers). Ceralasertib has shown significant activity in ARID1A-deficient endometrial cancer patients. This combination would have been a perfect fit for the patient based on DNA alterations present. The second trial I found offered ceralasertib as monotherapy.

Unfortunately, the first trial never responded to the patient’s email or calls, but she successfully enrolled in the second trial, with ceralasertib as monotherapy. Treatment for 5 months led to a 75% decrease in her serum cancer markers and a 45% decrease in tumor burden by RECIST criteria. Her response is ongoing.

Case 3: A 69-year-old woman was diagnosed with recurrence of HPV-related anal squamous carcinoma. She had initially been diagnosed with localized anal cancer 5 years earlier, which was treated with radiation and chemotherapy. In subsequent years she experienced 4 oligometastatic recurrences in lungs and one in the rectum, which were treated with surgeries, radiation, and chemotherapy. In 2019 three metastatic tumors were detected in her lungs.

I suggested some trials—including one known as Hestia—offering HPV E6/7 specific T cells (T cells isolated from peripheral blood and stimulated with HPV peptides). The patient has now undergone treatment in Hestia with a complete response, and remains disease-free almost 3 years later. Apparently, she was the only patient who had a durable response to this trial treatment.

Dr. Shtivelman can be reached at

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

People With Prostate Cancer See Their Journey Differently From Their Doctors

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

Nicole Jardine, BASc
Associate Manager, Patient Journey Analytics, Self Care Catalysts

Typical approaches to cancer research don’t necessarily capture the whole picture of what a patient might experience. Here, our Curious Dr. George asks Nicole Jardine, BASc, how real-world evidence can improve cancer research. Jardine is Associate Manager, Patient Journey Analytics at the company Self Care Catalysts, recently acquired by Alira Health.

Curious Dr. George: In your role at Self Care Catalysts, you have access to a trove of self-reported linear patient data—including treatment outcomes—from a large number of patients who, over several years, have used the Health Storylines Platform to manage their journey and generate real-world evidence. Can you share how this process provides notable insights?

Nicole Jardine, BASc: The science and research behind a particular disease are essential to prevent, diagnose, treat, maintain, or cure. But knowing a condition versus understanding the experience of someone with it are quite different. The research put into treating physical and mental health conditions is crucial to the medical field; however, treatment cannot truly progress without understanding the patient’s experience and their quality of life over time. When check-in appointments are the only time patients can share what is working and what is not, a disconnect arises between health personnel and the people they intend to help.

Real-world evidence presents an opportunity to understand decision-making and patient outcomes, providing more context to a patient’s journey. As a person who studies the in-depth experience of patients through de-identified quantitative and qualitative patient-reported data and structured interviews, I can say that supplementing this information is necessary to understand how to improve the ways we support and engage patients.

Part of my job includes comparing scientific literature to the holistic patient experience. Although they are comparable in some respects, the scientific literature does not capture the full experience patients have through interactions with the healthcare system. When you look at a patient’s experience, you are looking at every part—even what they experienced before their diagnosis—to get the full picture. A notable experience I had when doing research on a patient journey was looking at the experience of men with prostate cancer. When comparing the treatment experience of a person with prostate cancer to the literature on prostate cancer treatment, I saw a notable difference on how treatment efficacy is viewed. When literature reports positive outcomes on the efficacy of treatment, it’s seen as a good thing, but when a patient has decreased quality of life despite positive efficacy, where does that lead patients?

For patients, unless the benefits exceed the risks, quality of life trumps treatment compliance. In our patient database, we have 1,900 people with different forms of cancer, including 412 people with prostate cancer who use Health Storylines to track their experience. When we analyzed qualitative and quantitative Patient Reported Outcomes of these men, as well as five patient interviews, various themes emerged from the patient-reported treatment process, highlighting why treatment is not just about efficacy. The first theme is that oftentimes men are wary of speaking to their doctor regarding prostate cancer; it can be difficult to muster up the courage to even get to the doctor to talk about prostate cancer and feelings of worry about the experience. Men tend not to think about prostate cancer until they are diagnosed, so when deciding on treatment they care about their doctor’s opinion; however, that does not come at the expense of wanting to be heard throughout the process. Although men want to be heard and emotionally supported, they do not receive that support because it is often not talked about from the patient or the doctor’s side. Similarly, men are conditioned to be proud, and they struggle to report treatment side effects that hinder their quality of life because they feel misunderstood. This experience is overwhelming for them; it changes their life and perception of the healthcare system.

Understanding the holistic patient experience provides the opportunity to supplement clinical trials for prostate cancer treatment by displaying the experience men had, the variables around treatment persistence, the challenges men experience, what their needs are, how to support them, and what doctors should tell patients when recommending treatment. By not incorporating the authentic patient experience and opinion, the whole story is not being told. Capturing that whole story is necessary to inform future directions in treatment and create a community of patients who are confident in the system that is treating them.

Jardine can be reached at

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

A New Champion for Cancer Caregivers

Michael A. Looney, Ph.D.
Founder/Facilitator/Head Warrior at Courage Groups

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

Many people with advanced cancer can benefit from helpful caregivers, but family and friends who take on this role may have little background or training to do such a difficult job well. A new organization called Courage Groups aims to provide education and guidance in this collaborative journey. The founder is Mike Looney, PhD, a client and generous supporter of Cancer Commons, whose family recently established our Pat Looney Educational Series for Client Empowerment.

Curious Dr. George: What does Courage Groups offer and how may a caregiver best use these resources?

Mike Looney, PhD: It’s true, when a loved one receives an advanced cancer diagnosis, family and friend caregivers often just start “doing whatever is necessary.” In fact, many don’t even identify as “caregivers” per se; they often start in a passive role, performing such tasks as driving to appointments or picking up medications. But these passive caregivers have now entered the foreign and often bewildering world of medicine—and even worse: cancer.

In the world of cancer, there are new vocabularies, new experts with not-easily-understood specializations, competing treatment options, and built-in fear. This world is scary and intimidating. Regardless, it’s not uncommon that a caregiver will end up playing a vital role in the care of their loved one—typically without training, consultation, or guidance. Sometimes this role ends with making life-or-death decisions for a loved one with advanced cancer, and even administering treatment. Being a cancer caregiver is difficult, and it can also be a missed opportunity for the loved one’s primary cancer care team not to engage the caregiver early on.

Courage Groups was partially formed to assist caregivers in moving from passivity, confusion, and intimidation to confidence and engagement. The first thing that Courage Groups created is a Caregiver Dashboard. Like the dashboard in a car, it serves as a relatively quick snapshot to be referred to regularly about critical elements in the lives of the loved one and the caregiver. The dashboard’s mission is three-fold: 1) provide a road map (albeit different for every cancer and situation); 2) improve communication (among the caregiver, their loved one, the care team, and extended friends and family); 3) engage the caregiver as early as possible in the treatment plan.

The Dashboard is ideally used by the caregiver (and their loved one) to frequently assess the current status of the loved one across seven dimensions and subcategories: progression of disease, physical issues, pain management, participation in care decisions, attitude, communications, and wellbeing. Simultaneously, it asks the caregiver to rank four of those same dimensions and two that are specific to the caregiver: Their own support and issues relating to death and dying. The dashboard facilitates a quick analysis, and the caregiver can visually see where there is or is not alignment with their loved one, care team, or others. The potential benefits are greater confidence for the caregiver and improved comfort and communication for the loved one. There is also the real chance that outcomes for the loved one will be better: improved wellbeing, better treatment options pursued, side effects addressed faster, and more.

Courage Groups provides an online, free, short workshop on the Dashboard to help caregivers become familiar with the dimensions and subcategories, frequency of use, suggestions for addressing non-alignment, and more. Similarly, Courage Groups provides ongoing free online support and resource groups for caregivers by caregivers. These groups have a broad audience of caregivers not necessarily associated with any geography, hospital or cancer type. Current and former caregivers have “been there” and have great suggestions unique to the caregiver experience.

Caregivers are an untapped resource. Courage Groups’ mission is to champion and support these warriors.

Mike can be reached at

Using AI and Drug Testing to Design Personalized Cancer Drug Combos

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

Noah Berlow, PhD
Chief Technology Officer at First Ascent Biomedical, Assistant Member at Children’s Cancer Therapy Development Institute

Advanced cancer treatment often involves combining multiple drugs. But with a huge number of possible combinations, it is difficult to know which mix might work best for each patient. Here, our Curious Dr. George asks two leaders to describe how the company First Ascent Biomedical is addressing this challenge.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved many thousands of drugs for marketing, including many hundreds of drugs for use in treating cancer. Some of these drugs are effective; many are not. Many cancers remain without effective therapies. The opportunity to combine FDA-approved drugs offers an additional potential treatment for people with cancer. Many—even most—such combinations have not been rigorously tested.

How does your tumor profiling technology attempt to alleviate that gap and provide hope to cancer patients through combination therapies?

Diana Azzam, PhD, and Noah Berlow, PhD: The development of combination chemotherapy regimens was one of the earliest revolutions in cancer care that led to improved outcomes across nearly every cancer type. The power of drug combinations has been established by decades of clinical data, which is why 25% of oncology clinical trials are designed around drug combinations. Combination therapies are valuable to pharma as well since drug combinations allow for development of new IP and build additional value around assets.

But the driving challenge is always who, which, and when. Who needs which combination, and when? Given that the FDA has approved over 200 cancer drugs, there are over 19,000 possible 2-drug combinations, over 1.3 million 3-drug combinations, and 64 million 4-drug combinations. Setting up 19,000 clinical trials across every cancer type to explore every 2-drug combination is an intractable clinical problem, much less 3- or 4-drug combinations. Correspondingly, finding the right combination for the right patient at the right time is a profoundly difficult problem—but one that our technologies are working to address.

Our approach to this problem is driven first and foremost by functional drug testing, the process of testing a variety of anti-cancer drugs on live cancer cells derived from the patient’s own tumor. This process allows us to identify which drugs are more likely to be effective on the patient’s tumor. The unique way we perform drug sensitivity testing allows us to rapidly test more than 100 cancer agents on the patient’s cancer cells with a median 7-day turnaround time from tissue receipt to return of drug sensitivity results—both for solid and hematological cancers. This is fast enough to support clinical decisions for patients, especially those who have exhausted standard-of-care treatment options.

Our process primarily tests single drugs to identify which drugs show potential, which is where our artificial intelligence/machine learning (AI/ML) comes into play. The AI/ML platform uses the drug sensitivity data—which drugs worked, and which did not—and the patient’s genomic profile to identify multivariate mechanisms driving drug sensitivity. By understanding those critical vulnerabilities, identifying drug combinations becomes a matter of matching FDA-approved, clinically available drugs to the tumor vulnerabilities. We can then use the AI/ML to inform combination design, which, alongside physician input on combinations of interest, guides follow-up combination drug testing. The AI/ML enables us to close the feedback loop in drug combination testing for any cancer patient.

The AI/ML right now is focused on building a deep understanding of an individual patient. As we continue to work with new patients and accumulate more data, we plan to leverage the same AI/ML to identify patterns of patient response within cancer populations to support the development of drug combination studies or even monotherapy trials for the right population. We can support new trial development from insights built on drug response data from direct testing of hundreds or thousands of cancer patients, paving the way for more combination therapies for more cancer types, with a better understanding of who will respond and why.

Dr. Azzam can be reached at and Dr. Berlow at

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