Lung cancer is the leading cause of death worldwide for both men and women. Surgery can be offered as a radical treatment at stages I and II and selected cases of stage III (III A). Whereas at more advanced stages, combined modalities of treatment are applied: radiochemotherapy (IIIB) and molecularly targeted treatment (small molecule tyrosine kinase inhibitors, VEGF receptor inhibitors, monoclonal antibodies, and immunological treatment with monoclonal antibodies). Combination treatment, composed of radiotherapy and molecular therapy, is increasingly employed in locally advanced and metastatic lung cancer management. Recent studies have indicated a synergistic effect of such treatment and modification of immune response. The combination of immunotherapy and radiotherapy may result in the enhancement of the abscopal effect. Anti-angiogenic therapy, in combination with RT, is associated with high toxicity and should be not recommended. In this paper, the authors discuss the role of molecular treatment and the possibility of its concurrent use with radiotherapy in non-small cell lung cancer (NSCLC).

Skin melanomas are malignant neoplasms originating from neuroectodermal melanocytes. Compared to other neoplasms, melanomas have a high rate of growth. Their incidence is highest in Australia and New Zealand, in high‑income European countries (Switzerland, Norway, Sweden) and in the US. In Poland, the standardized incidence rate is approximately 5/100,000. Melanomas are typically highly radioresistant and chemoresistant. Before the era of immunotherapy, inoperable lesions were treated using chemotherapy based mainly on dacarbazine, temozolomide or fotemustine, which did not yield the expected results in terms of extending survival time or improving patient comfort. Therefore, there has emerged a need to seek other solutions. In most cases, the use of immunological treatment or targeted therapy has had a positive impact on survival time and relapse‑free survival. However, these periods are still relatively short, hence the need for further research and improvement of treatment. The most promising strategies appear to be antibodies that block programmed death receptor‑1 (PD‑1) and programmed death receptor ligand‑1 (PD‑L1) molecules, anti‑CTLA4 antibodies (cytotoxic T‑lymphocyte antigen 4) and therapy with BRAF and MEK inhibitors.

Changes in cell signaling pathways, which in normal conditions determine the maintenance of cell homeostasis and the correctness of its basic processes, may cause the transformation of a normal cell into a cancer cell. Alterations in cellular metabolism leading to oncogenesis are considered to be a hallmark of cancer cells. Therefore, a thorough understanding of cellular enzymes affecting metabolism and respiration, as well as intracellular pathways connected with them, seems crucial. These changes may be both prognostic and predictive factors, especially in terms of using molecularly targeted therapies. Aberrations in the pathways responsible for cell growth and angiogenesis are considered particularly important in the process of oncogenesis. Gliomas are the most common primary malignant tumors of the brain. The most important molecular disorders determining their particularly malignant nature are aberrations in the pathways responsible for cell growth and angiogenesis, such as the PI3K/Akt or RAS/MAPK/ERK signaling pathway, as well as excessive activity of enzymes, like hexokinases, which play a key role in glycolysis, autophagy, and apoptosis. The multitude of alterations detected in glioma cells, high heterogeneity, and the immunosuppressive environment within the tumor are the main features causing failures in the attempts to implement modern therapies.

The ability to undergo neoangiogenesis is a common feature with all cancers. Signaling related to vascular endothelial growth factors (VEGF) and their receptors (VEGFR) plays a key role in the process of tumor neoangiogenesis. A close relationship has been demonstrated between excessive VEGF levels and the induction of immunosuppression in the tumor microenvironment. The use of drugs blocking the VEGF function, apart from the anticancer effect, also result in adverse effects, in particular related to the circulatory system and kidneys. Cardiac toxicity associated with the use of such therapy manifests itself mainly in the form of hypertension, thromboembolic episodes and ischemic heart disease. In the case of renal complications, the most common symptoms include renal arterial hypertension, proteinuria and microangiopathy. Although these complications are reversible in 60–80% of cases after cessation of VSP (VEGF pathway inhibitor) therapy, in some cases they can lead to irreversible changes in renal function, whereas cardiac complications may be fatal. Also, the use of PD-1/PD-L1 inhibitors may result in kidney and heart damage. In the case of cardiac complications, the most common symptoms include myocarditis, pericarditis, arrhythmia, acute coronary syndrome and vasculitis, while kidney damage most often manifests as acute kidney injury (AKI), nephrotic syndrome, pyuria or hematuria. The decision whether to resume treatment after the occurrence of cardiovascular and renal complications remains a problem.

Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median follow-up was 31 months (6–108 months). The median PFS1 was 6 months (1–44 months). Second-line systemic treatment was applied in 27 patients (52%). The median PFS2 was 2 months (0–27 months), and the median OS was 31 months (6–108 months). Among the analyzed risk factors, only the presence of the BRAF mutation was statistically significant for disease recurrence after surgery. In patients undergoing anti-BRAF/MEK therapy, the median PFS1 was 7 months, and in patients undergoing mono-immunotherapy, 4 months. The 12- and 24-month PFS1 rates in the group treated with BRAF inhibitors were 29 and 7%, respectively, and in patients treated with mono-immunotherapy 13 and 0%, respectively (Z = 1.998, p = 0.04). The type of treatment used had no effect on OS (Z = 0.237, p > 0.05). Conclusion: Patients with the V600 mutation should be closely monitored. In the event of disease recurrence, treatment with BRAF/MEK inhibitors should be considered. The type of treatment used has no effect on OS.

Despite the initial clinical success of CDK4/6 inhibitors in combination with endocrine therapy, the development of resistance (intrinsic and acquired) remains a significant challenge in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). Recent advances have shed light on resistance mechanisms that primarily affect the cell cycle machinery, including loss of Rb function, cyclin E1 overexpression leading to CDK2 activation, and CDK6 or CDK4 upregulation. These alterations disrupt the G1/S checkpoint and drive proliferation independently of CDK4/6 inhibition. In contrast, non-cell cycle-related pathways, such as PI3K/AKT/mTOR and FGFR signaling, may also contribute but appear less central in many resistant tumors. These findings have highlighted the need for next-generation therapeutic approaches aimed at overcoming resistance. Selective inhibition of CDK2 and/or CDK4 is among the most promising strategies, potentially offering a more favorable therapeutic index while maintaining anti-proliferative efficacy. Early-phase trials of selective CDK2/CDK4 inhibitors, alone or combined, have shown encouraging activity, particularly in tumors resistant to prior CDK4/6 inhibition. However, most available data are limited to small, selected cohorts, underscoring the need for larger, randomized studies. Another emerging approach targets lysine acetyltransferases (KAT), key epigenetic regulators of transcription and cancer progression. KAT inhibition has shown potential to modulate oncogenic signaling and sensitize tumor cells to existing therapies, offering a complementary avenue for overcoming resistance. This review focuses on emerging cell cycle-centric mechanisms of resistance to CDK4/6 inhibitors and highlights innovative therapeutic strategies aimed at improving outcomes in HR+/HER2- mBC.