Folate Receptor Alpha-A Novel Approach to Cancer Therapy.

Folate receptor α (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is taken up by the cell via this receptor, which also targeted by many cancer agents due to the over-expression of the receptor by cancer cells. FR is a membrane-bound glycosyl-phosphatidylinositol (GPI) anchor glycoprotein encoded by the folate receptor 1 (FOLR1) gene. FR plays a significant role in DNA synthesis, cell proliferation, DNA repair, and intracellular signaling, all of which are essential for tumorigenesis. FR is more prevalent in cancer cells compared to normal tissues, which makes it an excellent target for oncologic therapeutics. FRα is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer. FR is widely used in antibody drug conjugates, small-molecule-drug conjugates, and chimeric antigen-receptor T cells. Current oncolytic therapeutics include mirvetuximab soravtansine, and ongoing clinical trials are underway to investigate chimeric antigen receptor T cells (CAR-T cells) and vaccines. Additionally, FRα has been used in a myriad of other applications, including as a tool in the identification of tumor types, and as a prognostic marker, as a surrogate of chemotherapy resistance. As such, FRα identification has become an essential part of precision medicine.

Special Issue "From Basic Science to Treatment Strategies: Personalized Cancer Therapy".

Molecular testing has created a revolution in cancer [...].

NTRK Therapy among Different Types of Cancers, Review and Future Perspectives.

Neurotrophic tyrosine receptor kinase (NTRK) has been a remarkable therapeutic target for treating different malignancies, playing an essential role in oncogenic signaling pathways. Groundbreaking trials like NAVIGATE led to the approval of NTRK inhibitors by the Food and Drug Administration (FDA) to treat different malignancies, significantly impacting current oncology treatment. Accurate detection of NTRK gene fusion becomes very important for possible targeted therapy. Various methods to detect NTRK gene fusion have been applied widely based on sensitivity, specificity, and accessibility. The utility of different tests in clinical practice is discussed in this study by providing insights into their effectiveness in targeting patients who may benefit from therapy. Widespread use of NTRK inhibitors in different malignancies could remain limited due to resistance mechanisms that cause challenges to medication efficacy in addition to common side effects of the medications. This review provides a succinct overview of the application of NTRK inhibitors in various types of cancer by emphasizing the critical clinical significance of NTRK fusion gene detection. The discussion also provides a solid foundation for understanding the current challenges and potential changes for improving the efficacy of NTRK inhibitor therapy to treat different malignancies.

Therapeutic Inertia and Treatment Intensification.

PURPOSE OF REVIEW: This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. RECENT FINDINGS: Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Integrative Therapies in Cancer Care: An Update on the Guidelines.

INTRODUCTION: ASCO and the Society for Integrative Oncology have collaborated to develop guidelines for the application of integrative approaches in the management of anxiety, depression, fatigue and use of cannabinoids and cannabis in patients with cancer. These guidelines provide evidence-based recommendations to improve outcomes and quality of life by enhancing conventional cancer treatment with integrative modalities. METHODS: All studies that informed the guideline recommendations were reviewed by an Expert Panel which was made up of a patient advocate, an ASCO methodologist, oncology providers, and integrative medicine experts. Panel members reviewed each trial for quality of evidence, determined a grade quality assessment label, and concluded strength of recommendations. RESULTS: Strong recommendations for management of cancer fatigue during treatment were given to both in-person or web-based mindfulness-based stress reduction, mindfulness-based cognitive therapy, and tai chi or qigong. Strong recommendations for management of cancer fatigue after cancer treatment were given to mindfulness-based programs. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. The recommended modalities for managing anxiety included Mindfulness-Based Interventions (MBIs), yoga, hypnosis, relaxation therapies, music therapy, reflexology, acupuncture, tai chi, and lavender essential oils. The strongest recommendation in the guideline is that MBIs should be offered to people with cancer, both during active treatment and post-treatment, to address depression. CONCLUSION: The evidence for integrative interventions in cancer care is growing, with research now supporting benefits of integrative interventions across the cancer care continuum.

Importance of ROS1 gene fusions in non-small cell lung cancer.

Targeted therapy has become one of the standards of care for advanced lung cancer. More than 10 genetic aberrations have been discovered that are actionable and several tyrosine kinase inhibitors (TKIs) have been approved to target each of them. Among several genetic aberrations that are actionable in non-small cell lung cancer (NSCLC), ROS1 translocations also known as gene fusion proteins, are found in only 1%-2% of the patient population. ROS1 mutations can usually be detected using a combination of techniques such as immunohistochemistry (IHC), Fluorescence in-situ testing (FISH), polymerase chain reaction (PCR), and next-generation sequencing (NGS). However, RNA NGS and ctDNA NGS (liquid biopsies) also contribute to the diagnosis. There are currently numerous FDA-approved agents for these tumors, including crizotinib and entrectinib; however, there is in-vitro sensitivity data and clinical data documenting responses to ceritinib and lorlatinib. Clinical responses and survival rates with these agents are frequently among the best compared to other TKIs with genetic aberrations; however, intrinsic or extrinsic mechanisms of resistance may develop, necessitating research for alternative treatment modalities. To combat the mechanisms of resistance, novel agents such as repotrectenib, cabozantinib, talotrectinib, and others are being developed. In this article, we examine the literature pertaining to patients with ROS1 tumors, including epidemiology, clinical outcomes, resistance mechanisms, and treatment options.

Diversity and Disparities in Lung Cancer Outcomes Among Minorities.

ABSTRACT: Because of diversities and disparities, lung cancer incidence and mortality rates among minorities are disproportionate compared with non-Hispanic White (NHW) populations. This review focuses on the disparities in lung cancer screening, diagnosis, treatment, and outcomes that minorities, mainly Hispanic and Black, experience compared with NHW populations. Despite efforts such as improving the eligibility criteria for screening to improve lung cancer survival rates, disparities persist, particularly among minority populations. However, the "Hispanic Paradox" describes the lower incidence and better survival rates observed in Hispanics compared with other ethnic groups best explained by possible contributions such as genetics and other factors such as dietary habits. Disparities in screening, particularly among underrepresented populations, are frequently explained by cultural, socioeconomic, and health care access barriers. There are also disparities in receiving appropriate treatment, such as surgical treatment, with fewer Hispanics and Blacks undergoing surgery than NHW individuals, resulting in lower overall survival rates. In addition, the prevalence of biomarker testing varies by racial and ethnic groups, influencing personalized treatment plans and outcomes. Finally, because of genetic and social determinants of health, the clinical outcomes of targeted therapy and immunotherapy may differ among minority populations. Identifying and addressing social determinants of health in real time are a "must" to have a significant impact in reducing lung cancer disparities. A comprehensive and multifaceted strategy is required to rectify disparities in cancer treatment. This strategy includes increasing levels of awareness and education, reducing financial and access barriers, and promoting increased diversity in clinical trial recruitment. By effectively addressing these complex challenges, the objective of providing equitable cancer care to all patients, regardless of race or ethnicity, can be achieved. To identify and address disparities, heightened awareness and education are essential. Access to health care is ensured by reducing financial and access barriers. Finally, increased diversity in clinical trial recruitment advances the generalizability of findings and promotes equitable representation of all racial and ethnic groups, resulting in improved outcomes for all patients.

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities.

INTRODUCTION: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities. METHODS: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender. RESULTS: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 - 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37-0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%). CONCLUSION: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage.