In this episode of MD Newsline, Dr. Jordonna Brown, a medical oncologist at Kings County Hospital in New York City, shares her frontline experience caring for patients in a safety-net hospital setting. Speaking from the San Antonio Breast Cancer Symposium (SABCS), Dr. Brown discusses cancer disparities, late-stage presentation, mistrust in the healthcare system, and the evolving landscape of breast cancer treatment.

She offers a candid look at the social determinants of health shaping patient outcomes—from delayed screening and misconceptions about chemotherapy to barriers in long-term adherence and clinical trial participation.

Late-Stage Presentation and Screening Gaps
Dr. Brown highlights a concerning trend: many patients present with advanced-stage breast cancer due to missed routine mammograms. Barriers include misconceptions about radiation exposure, fear of pain, religious beliefs, and lack of awareness about updated screening guidelines starting at age 40.

Mistrust and Chemotherapy Misconceptions
One of the most persistent challenges is distrust in the medical system. Patients often fear that chemotherapy may be more harmful than beneficial. Dr. Brown emphasizes the importance of patient-centered communication, empathy, and transparent education to build trust and empower informed decisions.

Younger Patients and Aggressive Disease
Breast and colon cancers are increasingly diagnosed in younger populations. In women under 40, breast cancer often demonstrates more aggressive tumor biology. Younger patients also face unique psychosocial challenges, including body image concerns, fertility considerations, career disruptions, and adherence to long-term maintenance therapy.

Socioeconomic Barriers and Access to Care
Financial instability, employment loss, transportation issues, and food insecurity can significantly impact adherence and long-term outcomes. Dr. Brown discusses how institutional support—such as social services, transportation programs, counseling, and food banks—helps mitigate these barriers.

Clinical Trials and Underrepresentation
Dr. Brown notes persistent skepticism around clinical trials among underrepresented communities. She underscores the need for improved education, emphasizing that today's standard treatments are the result of prior clinical trials—and that participation advances care for future generations.

Emerging Therapies and Personalized Medicine
At SABCS, Dr. Brown was encouraged by advances in early-stage hormone-positive breast cancer, including new selective estrogen receptor degraders (SERDs) such as giredestrant, which may offer improved tolerability compared to traditional endocrine therapies. She also discusses the growing role of artificial intelligence in shaping cancer care and the importance of ensuring diverse data representation in AI-driven tools.

Mental Health and Survivorship
The emotional and social impact of a cancer diagnosis often extends beyond treatment. Family dynamics, job security, and mental health are frequently under-addressed areas. Dr. Brown advocates for integrated palliative care, psychotherapy services, and survivorship groups to support patients holistically.

Addressing breast cancer disparities requires more than medical innovation—it demands trust-building, education, equitable access, and culturally sensitive communication. By partnering with patients, improving representation in clinical research, and strengthening community-based support systems, clinicians can meaningfully improve outcomes across diverse populations.

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In this episode of MD Newsline, Dr. Theodoros Karantanos, Assistant Professor of Medical Oncology at the Johns Hopkins University Sidney Kimmel Cancer Center, discusses the emerging role of inflammatory signaling in high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Dr. Karantanos shares insights from his laboratory research exploring how inflammatory pathways—particularly interferon gamma and JAK-STAT signaling—contribute to treatment resistance, including resistance to venetoclax. He also highlights the impact of TP53 mutations, bone marrow microenvironment dynamics, and post-translational modifications in shaping disease progression and therapeutic response.

Inflammatory Signaling and Venetoclax Resistance
High-risk MDS and AML frequently demonstrate upregulation of inflammatory pathways. Dr. Karantanos explains how interferon gamma signaling activates the JAK-STAT cascade (JAK1/2, STAT1/3/5), leading to transcriptional programs associated with resistance to venetoclax and chemotherapy.

The Role of TP53 in Driving Inflammation
Loss of TP53 function not only impairs apoptosis but may intrinsically upregulate interferon gamma signaling within leukemic cells. This cell-intrinsic inflammatory activation may partially explain why TP53-mutated MDS and AML remain particularly difficult to treat.

Post-Translational Modifications as Resistance Drivers
Phosphorylation and ubiquitination play central roles in regulating inflammatory cascades. Dr. Karantanos emphasizes that proteomic and phospho-signature analyses are essential, as RNA expression alone cannot fully capture pathway activation under therapeutic pressure.

Bone Marrow Microenvironment and Cytokine Crosstalk
The bone marrow niche—including fibroblasts, adipocytes, endothelial cells, and immune subsets—contributes to resistance through cytokine secretion (e.g., IL-1β, TNF-α) and drug metabolism. These interactions reshape therapeutic exposure and promote survival of malignant clones.

Monocytic Leukemias and Inflammatory Activation
Monocytic AML subtypes (M4/M5) appear particularly enriched in inflammatory signaling, including interferon gamma and TNF-α activation. These subsets may represent high-priority targets for inflammation-modulating strategies.

Targeting Inflammatory Pathways: Translational Strategies
Potential therapeutic approaches include IRAK1/IRAK4 inhibitors, JAK pathway modulation, and antibody-drug conjugates targeting downstream interferon-regulated surface proteins such as CCRL2 and ICAM-1. Combination and triplet regimens may offer future improvements over venetoclax-based standards.

Single-Cell and Spatial Transcriptomics
Dr. Karantanos highlights the importance of computational biology, single-cell RNA sequencing, and spatial transcriptomics in deciphering the complex inflammatory networks within the bone marrow microenvironment. These technologies are critical for identifying actionable nodes and refining patient stratification.

Inflammatory signaling is not merely a bystander in myeloid neoplasms—it is a central driver of disease evolution and therapeutic resistance. Integrating inflammatory biomarkers, post-translational pathway profiling, and microenvironmental analysis may unlock new precision strategies for high-risk MDS and AML, particularly in TP53-mutated and monocytic subtypes where unmet need remains greatest.

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In this episode of MD Newsline, Dr. Marco Ruella, Associate Professor of Medicine at the University of Pennsylvania and Scientific Director of the Lymphoma Program, joins us from the American Society of Hematology (ASH) meeting to discuss a paradigm-shifting topic: host factors in cancer immunotherapy.

Dr. Ruella explores how biological sex, aging, chronic inflammation, obesity, exercise, and the microbiome influence responses to therapies such as checkpoint inhibitors and CAR T-cell therapy. The conversation highlights emerging data, translational research, and the growing need to capture holistic patient information to optimize outcomes.

Why Host Factors Matter in Immunotherapy
Traditional clinical trials focus heavily on tumor biology, but host characteristics—including sex, age, metabolic state, and lifestyle—also shape immune responsiveness. Dr. Ruella explains how incorporating these variables can help explain why only a subset of patients achieve durable benefit.

Sex-Based Differences in Immune Response
Research suggests meaningful biological differences in cancer incidence, immune activation, and treatment outcomes between males and females. Female patients often demonstrate a more "inflamed" or "hot" tumor microenvironment, potentially contributing to stronger immune responses. Hormonal influences, X-linked immune genes, and lifestyle factors may all contribute.

Chronic vs. Acute Inflammation
Inflammation is a double-edged sword. While acute inflammation after therapy can enhance anti-tumor effects, chronic baseline inflammation is associated with poorer outcomes and greater toxicity in CAR T-cell therapy. Biomarkers such as ferritin, IL-6, CRP, and ESR may help stratify risk.

Aging and Biological Fitness
Chronological age alone does not predict immunotherapy outcomes. Instead, biological fitness and muscle mass (sarcopenia) may be more relevant predictors of response and toxicity. Emerging research aims to better define "biological age" to guide treatment decisions.

Microbiome, Diet, and Metabolism
Dr. Ruella shares compelling data linking gut microbiome diversity to CAR T-cell efficacy. Antibiotic exposure before therapy has been associated with poorer outcomes. Additionally, ketogenic diets and ketone bodies such as beta-hydroxybutyrate are being explored to enhance T-cell function in clinical trials.

Exercise as an Immune Modulator
Short-term exercise can mobilize NK cells and T cells into circulation, potentially priming the immune system before immunotherapy. Ongoing trials are investigating whether structured exercise programs may improve treatment efficacy.

AI, Wearables, and the Future of Data Capture
To fully understand host factors, clinicians must systematically collect data on diet, exercise, sleep, and inflammation. Wearables, mobile applications, and artificial intelligence may enable more comprehensive, multi-omic profiling and personalized immunotherapy strategies.

Cancer immunotherapy is not determined solely by tumor biology—it is profoundly shaped by the host. Sex differences, chronic inflammation, metabolic health, and lifestyle factors all influence immune function and treatment response. Integrating these variables into clinical research and real-world practice may unlock more precise, equitable, and effective immunotherapy strategies.

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Contact with Dr Marco Ruella: Here