Fibroblast Growth Factor receptor (FGFR) pathway aberrations have been implicated in approximately 7% of the malignancies. As our knowledge of FGFR aberrations in cancer continues to evolve, FGFR inhibitors emerged as potential targeted therapeutic agents. The promising results of pemigatinib and infigratinib in advanced unresectable cholangiocarcinoma harboring FGFR2 fusions or rearrangement, and erdafitinib in metastatic urothelial carcinoma with FGFR2 and FGFR3 genetic aberrations, lead to their accelerated approval by the United States (USA) FDA. Along with these agents, many phase II/III clinical trials are currently evaluating the use of derazantinib, infigratinib, and futibatinib either alone or in combination with immunotherapy. Despite the encouraging results seen with FGFR inhibitors, resistance mechanisms and side effect profile may limit their clinical utility. A better understanding of the unique FGFR-inhibitor-related toxicities would invariably help us in the prevention and effective management of FGFR-inhibitor-induced adverse events thereby enhancing their clinical benefit. Herein, we summarized the physiology of FGF/FGFR signaling and briefly discussed the possible mechanisms that could lead to FGFR inhibitor resistance and side effects. In addition, we proposed treatment guidelines for the management of FGFR-inhibitor-associated toxicities. This work would invariably help practicing oncologists to effectively manage the unique toxicities of FGFR inhibitors.

Hepatocellular carcinoma (HCC) is an aggressive malignancy accounting for 90% of primary liver malignancies. Therapeutic options for HCC are primarily based on the baseline functional status, the extent of disease at presentation and the underlying liver function that is clinically evaluated by the Barcelona-Clinic Liver Cancer system and Child–Pugh score. In patients with advanced HCC, the United States Food and Drug Administration (US-FDA) approved systemic therapies include the combination of atezolizumab–bevacizumab, sorafenib, and lenvatinib in the first line setting while cabozantinib, regorafenib, ramucirumab (in patients with alfa-fetoprotein [AFP] > 400 ng/mL), pembrolizumab, nivolumab, and nivolumab-ipilimumab combination are reserved for patients who progressed on sorafenib. European Medical Agency (EMA) approved the use of atezolizumab–bevacizumab, sorafenib, and lenvatinib in the first line setting, while cabozantinib, regorafenib, and ramucirumab (in patients with alfa-fetoprotein [AFP] > 400 ng/mL) are approved for use in patients that progressed on first-line therapy. In the first line setting, sorafenib demonstrated a median overall survival (OS) benefit of 3 months as compared to that of best supportive care in randomized phase III trials, while lenvatinib was shown to be non-inferior to sorafenib. Recently, phase 3 studies with immunotherapeutic agents including atezolizumab plus a bevacizumab combination and tremelimumab plus durvalumab combination demonstrated a better OS and progression free survival (PFS) compared to sorafenib in the first-line setting, making them attractive first-line options in advanced HCC. In this review, we outlined the tumorigenesis and immune landscape of HCC in brief and discussed the role and rationale of combining immunotherapy and anti-VEGF therapy. We further expanded on potential limitations and the future directions of immunotherapy in combination with targeted agents in the management of advanced HCC.

Endocrine disorders are known to involve all organ systems of the body, including the skin. The cutaneous manifestations of endocrine disorders can range from common findings such as acanthosis nigricans, pretibial myxedema, acne, hirsutism, hyper or hypopigmentation to rare cutaneous findings such as miliaria rubra, calciphylaxis, lentigines, and calcinosis cutis. These cutaneous symptoms can sometimes be the presenting symptoms or can even be pathognomonic of the underlying endocrine condition. In some cases, the cutaneous symptoms from an underlying endocrine abnormality may be the most prominent. These symptoms can significantly affect the quality of life of individuals. Often, individuals may seek health care from a dermatologist or primary care physician for isolated skin symptoms. Therefore, it is imperative for physicians to recognize the skin symptoms as the manifestation of the endocrine disorder for prompt diagnosis and treatment of the underlying endocrine disorder.

Aspirin and statin drugs have been associated with reduced risk of several gastrointestinal cancers, but their association with gallbladder cancer (GBC) has not been well established. We evaluated the association of aspirin and statins with the risk of GBC. Patients with GBC managed at Mayo Clinic between 2000 and 2019 were matched 1:2 with a general patient pool by age and sex. Univariable and multivariable logistic regression models were used to assess associations between GBC and aspirin or statin use. The analysis included 795 cases and 1590 controls, with a median age of 67 years. Aspirin or statin use alone or in combination was higher in controls (p < 0.001). Univariate analysis showed that the use of aspirin [odds ratio (OR): 0.11; 95%CI: 0.08–0.15] or statins (OR: 0.29; 95%CI: 0.20–0.40) and their combined use (OR: 0.18; 95%CI: 0.13–0.24) was associated with lower risk of GBC. Multivariable analysis revealed that aspirin (OR: 0.12; 95%CI: 0.09–0.16) and combined statins and aspirin (OR: 0.46; 95%CI: 0.31–0.67) were associated with lower risk of GBC. Aspirin alone or in combination with statins is associated with a strongly reduced risk of GBC. Further prospective studies are needed to confirm these results and to elucidate their mechanisms.