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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. [ABSTRACT FROM AUTHOR]

The article discusses a systematic review on the adverse effects of immune checkpoint inhibitors for cancer treatment. Topics include the occurrence of adverse events in any organ during treatment and after discontinuation of the inhibitors, the administration of corticosteroids for grade 2 or higher reactions as the most important step in managing immune-related adverse events and the need to conduct research on the predictive biomarkers of immune-related adverse events and their management.

The article presents a case study of a 59-year-old woman who undergo a full septic workup and broad-spectrum antibiotics and intravenous (IV) hydration due to coma and dysautonomia. It mentions that the patient has a widely metastatic colon cancer who participates in a programmed cell death ligand 1 inhibitor atezolizumab's clinical trial. It discusses the condition which was commonly caused by diffuse cerebritis.

The article presents a case study of a 50-year-old man with metastatic colon cancer. He was treated with third-line pembrolizumab after disease progression by folinic acid, fluorouracil, and oxaliplatin. He was also diagnosed with mild psoriasis and received treatment by inhibiting interaction of cytokine with the interleukin-17 receptor.

The article offers information about the Janus kinase (JAK) inhibitor tofacitinib as a new therapeutic strategy for patients with ulcerative colitis refractory to biologic agents. It discusses the use of tofacitinib in a patient who had mismatch repair-deficient gastric cancer. It mentions the JAK-STAT, a regulatory signaling pathway that integrates cues from both innate and adaptive immunity.

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. [ABSTRACT FROM AUTHOR]

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors which activate the host's immune system to fight cancer have brought dramatic improvements to the overall survival of a growing number of deadly malignancies. Their use comes at the expense of often serious immune-related adverse events which consist of an off-target attack of the immune system on potentially any of the human body's healthy organs. For lack of better-validated evidence, and regardless of the organ affected, clinicians often use the same immunosuppressive regimens consisting of high dose corticosteroids followed by the introduction of biologic agents such as the tumor-necrosis alpha inhibitor infliximab for corticosteroid-refractory toxicities. The article by Johnson et al. is timely in providing a more personalized approach for the management of immune-related toxicities affecting the lower digestive tract with many positive clinical outcomes associated with the upfront use of infliximab in association with corticosteroids. This commentary will provide a narrative summary of their findings in light of the current clinical knowledge relevant to the understanding of immune-related enterocolitis. [ABSTRACT FROM AUTHOR]

Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P =.027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients. [ABSTRACT FROM AUTHOR]

Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Although cure rates are high, survivorship can be linked with significant long-term morbidity associated with both chemotherapy and radiotherapy. The most significant recent advances have been with the use of the anti-CD30-drug conjugated antibody brentuximab vedotin (BV) and inhibitors of program death 1 (PD-1). HL is genetically wired to up-regulate program death ligand 1 (PD-L1) in >95% of cases, creating a state of so-called “T cell exhaustion”, which can be reversed with immune checkpoint-inhibitor blockade. The overall and complete response rates to PD-1 inhibitors in patients with relapsed or refractory HL are 70% and 20%, respectively, with a long median duration of response of ~16 months. In fact, PD-1 inhibitors can benefit a wide spectrum of relapsed HL patients, including some who have “progressive disease” by strict response criteria. We review the biology of HL, with a focus on the immune micro-environment and mechanisms of immune evasion. We also provide the rationale supporting the use of PD-1 inhibitors in HL and highlight some of the challenges of monitoring disease response in patients treated with this immunotherapy. [ABSTRACT FROM AUTHOR]

The article presents a case study of 59-year old man suffering from stage IV melanoma being treated with first-line ipilimumab and nivolumab. It discusses the late development of rash which was treated with topical corticosteroids, but failed and then, again treated with systemic corticosteroids. It also talks about the patient contracting grade 2 hepatitis.

Background: Preclinical models have reported a synergistic interaction between sorafenib and vinorelbine. We investigated the toxicity, efficacy, and pharmacokinetics interaction of this combination as first-line treatment for patients with metastatic breast cancer. Methods: Patients were HER2-negative and treated with vinorelbine 30 mg/m2 IV days 1,8 every 21 plus daily oral sorafenib. In the phase I portion (3+3 design) patients received sorafenib 200 mg BID (cohort 1) or 400 mg BID (cohort 2). In the phase II expansion, 21 more evaluable patients were planned to receive the maximum tolerated dose (MTD). Pharmacokinetic analysis was performed in 6 patients: blood concentrations were compared for each drug in the presence or absence of the other drug. Results: In cohort 1, one patient experienced a dose-limiting toxicity (DLT) (grade 3 pancreatitis), requiring the expansion of this cohort to 6 patients, without further documented DLTs. In cohort 2, one patient of six experienced a grade 4 DLT (asymptomatic rise in amylase not requiring drug discontinuation), establishing this dose level as the MTD (sorafenib 400 mg BID). After expansion at the MTD, a total of 27 patients (median age 57) were treated for a median of 8 cycles. One grade 5 febrile neutropenia occurred. With repeated cycles, 52% of patients required at least 1 dose reduction of either drug. One patient experienced a sustained grade 3 fatigue resulting in treatment discontinuation. The response rate was 30%. Median PFS was 5.7 months (95% CI 4.4–7.6), and clinical benefit (absence of disease progression at 6 months) was 48%. PK analysis showed a significant interaction between the two drugs, resulting in a higher Cmax of vinorelbine in the presence of sorafenib. Conclusion: The combination of sorafenib and vinorelbine at full doses is feasible but not devoid of toxicity, likely also due to a significant PK interaction. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]