Cancer immunotherapy in the form of immune checkpoint inhibitors has led to a dramatic increase in the survival of patients with lung cancer across all stages. Over the past decade, the field has experienced rapid maturation; however, several challenges continue to complicate patient management. This review aims to highlight the data that led to this dramatic shift in practice as well as to focus on key challenges. These include determining the optimal therapy duration, managing frail patients or those with brain metastases, addressing the challenges posed by immune-related adverse events, and defining the various patterns of clinical and radiological responses to immunotherapy.

Camu camu (CC) is a prebiotic that selectively stimulates growth and activity of beneficial gut microbiota. Work in murine models demonstrated that castalagin, the active compound in CC, preferentially binds to beneficial gut microbiome bacteria, promoting a stronger CD8+T cell anti-cancer response. We present two patients with metastatic melanoma whose cancer progressed on immune checkpoint inhibitors (ICIs) and developed clinically significant immune-related adverse events (irAEs). They were rechallenged with ICIs in combination with CC. The first patient is a 71-year-old woman with metastatic melanoma, whose ICI treatment was complicated by immune-related pneumonitis and colitis. Upon progression on maintenance nivolumab, CC was added to nivolumab, leading to a near complete response (CR). The second patient is a 90-year-old man with recurrent unresectable melanoma, treated with nivolumab, complicated by immune-related rash and diabetes. He developed new subcutaneous calf lesions and a metastatic popliteal lymph node. CC was added to nivolumab. One month later, the patient experienced a CR. Both patients have been on nivolumab and CC with durable responses for more than a year, with minimal irAEs. These two cases suggest that CC may modulate the microbiome, synergizing with ICIs to produce deep, durable responses with minimal irAEs.

In the past decade, a lot of insight was gathered into the composition of the host and tumor factors that promote oncogenesis and treatment resistance. This in turn has led to the ingenious design of multiple new classes of drugs, which have now become the new standards of care in cancer therapy. These include novel antibody-drug conjugates, chimeric antigen receptor T cell therapies (CAR-T), and bispecific T cell engagers (BitTE). Certain host factors, such as the microbiome composition, are also emerging not only as biomarkers for the response and toxicity to anti-cancer therapies but also as potentially useful tools to modulate anti-tumor responses. The field is slowly moving away from one-size-fits-all treatment options to personalized treatments tailored to the host and tumor. This commentary aims to cover the basic concepts associated with these emerging therapies and the promises and challenges to fight cancer.

Metastatic clear cell renal cell carcinoma (ccRCC) remains largely incurable, and the efficacy of pembrolizumab plus axitinib may be limited by hypoxia-associated signaling, immunosuppressive cytokines, and metabolic reprogramming involving the TGF-β1/HIF axis. Seleno-L-methionine (SLM) is a pharmacologic inhibitor of this axis and its downstream effectors, including PD-L1 and VEGF. In a phase I/II pilot study (ClinicalTrials.gov NCT05363631), patients with newly diagnosed metastatic ccRCC received SLM twice daily for 14 days, then once daily with standard-dose axitinib; pembrolizumab was added on day 15. Endpoints included circulating (plasma) TGF-β1, plasma selenium, circulating cytokines, efficacy, and safety. Twelve patients were treated and evaluable for safety (six at 5000 µg, six at 6000 µg SLM); ten were evaluable for response. The objective response rate was 70% (complete response 40%, partial response 30%). Of the four patients with CR, two had favorable and two had intermediate International Metastatic Renal Cell Carcinoma Database Consortium disease. Grade 3 hypertension was documented in 58.3%, about twice the pivotal-trial rate, without treatment discontinuations or new toxicities. SLM increased plasma selenium and produced time-dependent inhibition of TGF-β1 and modulation of immune-related cytokines (CXCL13, IFN-γ, TNF-α, IL-6, IL-8). In this pilot study, SLM combined with axitinib and pembrolizumab showed time-dependent TGF-β1 inhibition, cytokine modulation, and encouraging antitumor activity without treatment-limiting toxicity, supporting further investigation of SLM for targeting the TGF-β1/HIF-driven immunosuppressive microenvironment in ccRCC.

Introduction The present study was designed to compare the treatment provided in private and public health care facilities for women positive for early breast cancer of the human epidermal growth factor receptor 2 (HER2) subtype, who received anti-HER2 therapy in neoadjuvant or adjuvant settings, with an evaluation of the recurrence-free survival (RFS) and pathological complete response (pCR) rates. Materials and Methods The current is a retrospective study carried out at the Instituto Brasileiro de Controle do Cancer (IBCC Oncologia), in the city of São Paulo, Brazil. We included patients treated between 2015 and 2020. Results The study included 472 medical records of early HER2-positive breast cancer patients treated in the public and private health care systems who received neoadjuvant or adjuvant treatments. The pathological complete response (pCR) was related to a lower recurrence rate and a longer recurrence-free survival (RFS). The results showed no statistically significant difference between the public and private health care systems in terms of RFS. Discussion Although the public health care patients were diagnosed with more advanced diseases than the private health care patients, both presented similar survival rates. In spite of the small number of patients evaluated, the dual HER2 blockade did not improve the clinical outcomes. These findings should be confirmed through studies with a larger number of patients and a longer follow-up period.