The year 2023 witnessed a significant revolution in oncology, marked by the emergence of new anti-cancer molecules and innovative strategies.

Antibody conjugates have considerably improved patient survival in numerous cancer types. These treatments are likely to play a key role in advanced-stage disease of urothelial cancers and in several breast cancer types as well, including triple-negative, HER2-positive, and a new entity known as “HER2 weak”.

Considering renal cancer, targeting the HIF transcription factor by means of a targeted therapy that inhibits not only angiogenesis, but also various survival pathways, looks rather promising. This novel therapeutic strategy can be administered either as a single agent or in combination.

Uveal melanoma is the most common primary malignant intraocular tumor. Despite the efficacy of local treatments, half of all affected patients experience extra-ocular recurrence, with liver involvement observed in 90% of them. Median survival for patients with metastatic disease has been proven to range between 6 and 12 months. Targeted treatments, such as thermo-ablation or surgery, likely improve the prognosis of patients with single-site recurrences. Chemotherapy is not very effective. Treatment with immune checkpoint inhibitors, such as anti-PD-1 antibodies, only modestly increases overall survival in metastatic disease patients. Tebentafusp, a new form of immunotherapy, is the first molecule to demonstrate a real improvement in overall survival of metastatic patients. Tebentafusp is a T-cell receptor coupled with an anti-CD3 antibody, being able to transform all lymphocytes into anti-melanocyte lymphocytes. Nevertheless, only patients with an HLA-A*02:01 allele, meaning 50% of Caucasians, are likely to benefit from this therapeutic innovation.

Myelofibrosis is a myeloproliferative neoplasm with a poor survival rate, primarily characterized by anemia, splenomegaly, constitutional symptoms, bone pain, and cachexia. The only curative treatment is allogeneic peripheral stem cell transplantation, although it is associated with a non-negligible mortality and morbidity risk. JAK2 inhibitors help reduce spleen size and alleviate symptoms in these patients. The two most recent JAK2 inhibitors (pacritinib and momelotinib) may also confer erythropoietic benefits.

Despite therapeutic advances in multiple myeloma management, the disease remains incurable, largely due to the emergence of resistant tumor clones. Immunotherapy has made significant progress in recent years. In front-line therapy, the inclusion of monoclonal antibodies alters the outcomes for transplant-eligible patients, providing potential long-term disease control. In relapse, bispecific antibodies and CAR-T cells demonstrated notable efficacy in terms of survival and residual disease control, offering real hope for patients resistant to conventional treatments. These two aspects will be addressed in this article.

In patients presenting with venous or arterial thrombosis associated with thrombocytopenia, the presence of anti-PF4 antibodies and their properties (heparin dependence and platelet activation capacity) should be investigated. Widely adopted in congenital hemophilia, emicizumab, a bispecific antibody mimicking the action of factor VIII, is poised to become a first-line hemostatic treatment for patients with acquired hemophilia. These patients will benefit from better protection against bleeding, delaying the onset of severe and often deleterious immunosuppression in fragile patients. Certain intravenous iron formulations may lead to hypophosphatemia, a neglected but avoidable complication. For refractory forms of autoimmune thrombocytopenia, complement, Bruton's tyrosine kinase, CD38, and the neonatal Fc receptor represent promising therapeutic targets.