The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.

Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to improve the efficacy of PDT without significantly increasing the risks of side effects have been proposed. In this study, we reviewed the combination-based PDT treatments described in the literature for treating AKs; both post-treatment and pretreatment were considered including topical (i.e., diclofenac, imiquimod, adapalene, 5-fluorouracil, and calcitriol), systemic (i.e., acitretin, methotrexate, and polypodium leucotomos), and mechanical–physical (i.e., radiofrequency, thermomechanical fractional injury, microneedling, microdermabrasion, and laser) treatment strategies. Topical pretreatments with imiquimod, adapalene, 5-fluorouracil, and calcipotriol were more successful than PDT alone in treating AKs, while the effect of diclofenac gel was less clear. Both mechanical laser treatment with CO₂ and Er:YAG (Erbium:Yttrium–Aluminum–Garnet) as well as systemic treatment with Polypodium leucotomos were also effective. Different approaches were relatively more effective in particular situations such as in immunosuppressed patients, AKs in the extremities, or thicker AKs. Conclusions: Several studies showed that a combination-based approach enhanced the effectiveness of PDT. However, more studies are needed to further understand the effectiveness of combination therapy in clinical practice and to investigate the role of acitretin, methotrexate, vitamin D, thermomechanical fractional injury, and microdermabrasion in humans.

Background: Facial atrophic acne scars have a significant impact on patients’ psychosocial well-being and remain a therapeutic challenge. Existing treatments options are frequently limited by modest efficacy and adverse effects. The combination of Polynucleotide High-Purification Technology (PN HPT™) and hyaluronic acid (HA) represents a novel bioregenerative strategy aimed at improving dermal remodelling and overall skin quality. Methods: This six-month, prospective, real-world study evaluated the efficacy and safety of Newest^® (Mastelli S.r.l., Sanremo, Italy), a sterile intradermal gel containing highly purified polynucleotides (10 mg/mL) and HA (10 mg/mL). Eligible participants, aged 20–60 years with moderate-to-severe atrophic facial post-acne scars, underwent four treatment sessions in two-week intervals. Efficacy was assessed using the Acne Scar Assessment Scale (ASAS) and Global Aesthetic Improvement Scale (GAIS) at three and six months, while safety was monitored throughout the study. Results: A total of 62 patients (32 Caucasian, 30 Asian; 19 males, 43 females; mean age: 36.6 years) completed the study. At three and six months, 46.8% showed at least a one-grade reduction in ASAS score with respect to the baseline. Patient-reported GAIS indicated that 54.8% perceived an improvement in scar appearance, aligning with investigator assessments. Only one mild, transient adverse event (wheal formation) occurred, which resolved spontaneously without intervention. Conclusions: In this real-world study, treatment with Polynucleotide High-Purification Technology (10 mg/mL) combined with HA (10 mg/mL) was associated with observable improvementin atrophic facial acne scars, with an excellent safety and tolerability profile. These findings support the potential of polynucleotide-based therapies for use as well-tolerated options for managing moderate-to-severe atrophic acne scarring, while the need for further controlled studies to confirm efficacy is also acknowledged.