The term "undruggable" is used to describe a protein that is not pharmacologically capable of being targeted; recently, however, substantial efforts have been made to turn these proteins into "druggable" targets. Thus, "difficult to drug" or "yet to be drugged" are perhaps more appropriate terms. In cancer, a number of elusive targets fall into this category, including transcription factors such as STAT3, TP53, and MYC. Pharmacologically targeting these intractable proteins is now a key challenge of modern drug development, requiring innovation and the development of new technologies. In this article, we discuss some of the recent technologic and pharmacologic advances that have underpinned the erosion of the concept of undruggability. We describe recent successes in drugging the undruggable RAS (KRAS G12C and HRAS), and discuss the advances that have led to the validation of further targets previously believed to be undruggable, such as HIF-2α, BCL-2, MDM2, and MLL. Finally, we look to the future and describe important advances that are likely to have a major impact on targeting undruggable targets, such as the advent of proteolysis-targeting chimeras and protein-protein modulators, which are leading to considerable excitement surrounding the development of cancer targets.At the time of writing, five anti-CD19 CAR T-cell products are approved by the U.S. Food and Drug Administration for seven different indications in lymphoid malignancies, including B-cell non-Hodgkin lymphoma, pediatric B-cell acute lymphoblastic leukemia, and multiple myeloma. CAR T cells for chronic lymphocytic leukemia, acute myeloid leukemia, and less common malignancies such as T-cell lymphomas and Hodgkin lymphoma are being tested in early-phase clinical trials worldwide. The purpose of this overview is to describe the current landscape of CAR T cells in hematologic malignancies, outline their outcomes and toxicities, and explain the outstanding questions that remain to be addressed.Adoptive cell therapy has significantly impacted the immuno-oncology landscape. The number of strategies currently in preclinical and clinical development is increasing at a rapid rate. Indeed, we are experiencing a transformative movement in cancer care as we shift toward highly personalized treatments designed to confront the specific challenges of each cancer. Advancements in genetic engineering methods and single-cell profiling technologies provide a level of understanding of the interactions between the immune system and cancer never before achieved. This knowledge, in turn, can be applied to the design and engineering of effective cancer-fighting treatments. As these promising new therapies progress toward clinical application, it becomes evident that we must develop robust methods for production and validation of cellular products to ensure consistency, safety, and efficacy, irrespective of cell type or indication. Herein, we provide an overview of the innovative approaches guiding the new generation of cell therapies and describe the benefits and challenges associated with emerging autologous and allogeneic platforms. Moreover, we discuss important considerations pertaining to process development, cost of goods, and manufacturing, and highlight their impact on the transfer of therapies from bench to bedside.There are well-known racial/ethnic disparities in the prevalence of obesity and physical inactivity, as well as breast cancer risk and survival. However, most of the current scientific evidence that serves as a foundation for nutrition and physical activity guidelines is based on studies conducted in predominantly non-Hispanic White populations. Similarly, exercise, diet, or lifestyle intervention trials for breast cancer prevention and survivorship are scarce in racial/ethnic minority populations. We review the current evidence for racial/ethnic disparities in obesity and breast cancer risk and survival (we are focusing on obesity, because this is considered an ASCO priority, and studies conducted in the United States), discuss the evolution of nutrition/physical activity guidelines for cancer prevention and control, and provide an overview of lifestyle interventions, including barriers and facilitators in implementation and dissemination science among minority populations underrepresented in research. There is a critical need to include racially/ethnically diverse populations in cancer prevention and control research or to specifically target minority populations in which disparities are known to exist to achieve much needed health equity.The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported.  https://www.selleckchem.com/products/jsh-150.html  In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.More than 90% of women with newly diagnosed breast cancer present with stage I to III disease and, with optimal multidisciplinary therapy, are likely to survive their disease. Of these patients, 70% are hormone receptor-positive and candidates for adjuvant endocrine therapy. The adoption of cumulatively better adjuvant treatments contributed to improved outcomes in patients with hormone receptor-positive, early-stage breast cancer. Premenopausal women with hormone receptor-positive breast cancer often present with complex disease and have inferior survival outcomes compared with their postmenopausal counterparts. Risk stratification strategies, including classic clinicopathologic features and newer gene expression assays, can assist in treatment decisions, including adjuvant chemotherapy use and type or duration of endocrine therapy. Gene expression assays may help identify patients who can safely forgo chemotherapy, although to a lesser extent among premenopausal patients, in whom they may play a role only in node-negative disease.