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Massimiliano Berretta

Publications and source records attributed to Massimiliano Berretta.

At least 19 recordsLinked to original sources
PubMed2026

PIK3CA in Cancer: Structure, Biology, Alterations, and Actionability.

PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), is one of the most frequently altered oncogenes in human cancer and a major driver of tumor initiation, progression, metastasis, and therapeutic resistance. Over the past two decades, advances in structural biology, cancer genomics, and translational research have substantially expanded our understanding of PIK3CA function and established the PI3K pathway as a clinically actionable therapeutic target. This review provides an overview of the structural organization and physiological functions of the PI3Kα complex, the molecular mechanisms underlying oncogenic activation, and the diverse spectrum of PIK3CA alterations across human malignancies. We also summarize the current landscape of PI3K-targeted therapies, highlighting both approved agents and emerging therapeutic strategies. Clinical evidence supports the rational integration of PI3K inhibitors with endocrine therapy, CDK4/6 inhibitors, MAPK pathway inhibitors, dual PI3K/mTOR inhibition, and immune checkpoint blockade. In addition, accumulating evidence indicates that PIK3CA plays a pivotal role in shaping the tumor immune microenvironment, providing a biological rationale for combining PI3K inhibition with immunotherapy. Finally, we discuss future directions in precision oncology, emphasizing integrated molecular profiling, liquid biopsy, single-cell and spatial technologies, functional genomics, and evolutionary approaches as complementary strategies to refine patient selection, overcome therapeutic resistance, and optimize clinical outcomes.

PI3K signaling↗
PubMed2026

Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.

BACKGROUND: DNA mutations are the fundamental engines of cancer, driving its initiation and progression. The forces that fuel malignancy are also the architects of evolution, shaping life through genetic variations. Mutations, in fact, can emerge naturally from endogenous processes, such as oxidative DNA damage or errors in replication, as well as induced by external factors, including cosmic radiation and chemical carcinogens. MAIN BODY: A key question in cancer research is whether tumor evolution is primarily governed by selective bottlenecks, neutral evolution, or dynamic genetic plasticity. In this work, we examine cancer as a disease driven by evolutionary processes rooted in fundamental biological requirements, including sustained proliferation and nutrient utilization. We hypothesize that the accumulation of mutations activates an evolutionary switch, enabling tumor cells to acquire an enhanced capacity for survival, adaptation, and growth at rates far exceeding typical evolutionary timescales. We propose the "evolutionary cascade hypothesis," a unifying framework that integrates these models into a coherent sequence. At its core lies the failure of DNA repair mechanisms, representing a critical transition in cancer progression. This shift marks the transition from an initial non-Darwinian, neutral phase to a Darwinian, more deterministic phase. CONCLUSIONS: As predictive models of tumor evolution advance through genomic big data and artificial intelligence-driven analysis, the future of cancer treatment may extend beyond targeting individual mutations to disrupting the underlying evolutionary mechanisms that sustain malignancy. This paradigm shift could redefine therapeutic strategies and ultimately improve patient outcomes.

Humans↗
PubMed2006

Hepatitis C virus in elderly cancer patients.

BACKGROUND: There are few studies about the relationship between HCV and the development of other tumors. We consider the prevalence of HCV infection in elderly cancer patients who have tumors different from that in hepatocellular carcinoma and non-Hodgkin's lymphoma. METHODS: We evaluated the prevalence of HCV infection in 236 elderly cancer patients in comparison with 300 elderly volunteers. Cancer patients presented a variety of tumors other than hepatocarcinoma and lymphoma, namely, colorectal (n=66), breast (n=44), bladder (n=40), prostate (n=30), lung (n=22), kidney (n=15), pancreatic (n=6), thyroid (n=5), cervical (n=4), melanoma (n=3) and vaginal (n=1). RESULTS: Among the 236 elderly cancer patients, 87 were positive for HCV antibodies (36%) and, among the 300 elderly patients, 32 were positive (10%). A comparison between the two groups revealed a statistically significant difference (p<0.001) between patients with kidney cancer, bladder cancer or prostate cancer, and the control group. CONCLUSIONS: The high anti-HCV prevalence in elderly cancer patients may be due to several mechanisms. These patients are more prone to acquire an HCV infection because of their frequent hospitalizations and the immunological changes in patients with tumors may lower their threshold for HCV infection.

Journal Article↗
PubMed2004

Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials.

Evidence suggests that infusional therapy is a more effective means for administering cytotoxic therapy than intravenous bolus therapy for lymphoma and offers greater potential for therapeutic synergy with rituximab, which has a long half-life. We pooled the results of 3 prospective phase 2 trials evaluating rituximab in combination with 96-hour infusion of cyclophosphamide (187.5-200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (R-CDE) plus granulocyte-colony-stimulating factor (G-CSF) in 74 patients with HIV-associated, B-cell non-Hodgkin lymphoma, of whom 56 (76%) patients received concurrent highly active antiretroviral therapy (HAART). The complete remission (CR) rate was 70% (95% confidence interval [CI], 59%-81%), and the estimated 2-year failure-free survival and overall survival rates were 59% (95% CI, 47%-71%) and 64% (95% CI, 52%-76%), respectively. Ten (14%) patients had opportunistic infections during or within 3 months of the end of R-CDE, and 17 (23%) patients developed nonopportunistic infections after that time. Six (8%) patients died because of infection; 2 (3%) of those infections were bacterial sepsis during R-CDE, and 4 (5%) were opportunistic infections that occurred between 2 and 8 months after the completion of R-CDE. R-CDE produced a 70% CR rate and a 59% 2-year failure-free survival rate in patients with HIV-associated lymphoma. Consistent with other reports, adding rituximab to cytotoxic therapy in this population may increase the risk for life-threatening infection. Further studies evaluating rituximab in combination with infusional chemotherapy are warranted, but caution is advised.

Adult↗
PubMed2004

CD90/Thy-1 is preferentially expressed on blast cells of high risk acute myeloid leukaemias.

Different transformation mechanisms have been proposed for elderly acute myeloid leukaemia (AML) and secondary AML (sAML) when compared with de novo AML or AML of younger patients. However, little is known regarding differences in the immunophenotypic profile of blast cells in these diseases. We systematically analysed, by flow cytometry, 148 patients affected by de novo (100 cases) or sAML (48 cases). By defining a cut-off level of 20% of CD34+ cells co-expressing CD90, the frequency of CD90+ cases was higher in sAML (40%) versus de novo AML (6%, P < 0.001), elderly AML (>60 years) (24%) versus AML of younger patients (10%, P = 0.010) and poor- versus good-risk karyotypes (according to the Medical Research Council classification, P < 0.001). The correlation between CD90 expression, sAML and unfavourable karyotypes was confirmed by analysing the subset of CD34+ AML cases alone (91/148). Consistently, univariate analysis showed that expression of CD90 was statistically relevant in predicting a shorter survival in CD90+ AML patients (P = 0.042). Our results, demonstrating CD90 expression in AML with unfavourable clinical and biological features, suggest an origin of these diseases from a CD90-expressing haemopoietic progenitor and indicate the use of CD90 as an additional marker of prognostic value in AML.

Acute Disease↗
PubMed2004

Mutational status of IgVH genes consistent with antigen-driven selection but not percent of mutations has prognostic impact in B-cell chronic lymphocytic leukemia.

Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes, along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to confirm the prognostic value of the IgVH gene mutational status by using the suggested cutoff. However, the IgVH mutational status maintained its prognostic value only when evidence of antigen-driven selection could be documented. This was accomplished by applying statistical methods aimed at evaluating a significant skewing of replacement mutations from framework to complementary determining regions, as it occurs during germinal center differentiation of B cells. These data caution against wide application of the 2% somatic mutation cutoff as a prognostic determinant without demonstration of antigen-driven selection.

ADP-ribosyl Cyclase↗
PubMed2003

Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma.

BACKGROUND: The objective of the current study was to evaluate the impact of highly active antiretroviral therapy (HAART) on clinical characteristics of presentation and the natural history of Kaposi sarcoma (KS) in patients already receiving HAART at the time of KS diagnosis. METHODS: The authors conducted a retrospective cohort study comparing epidemiologic, clinical, and outcome data for 160 patients who were naive to HAART at the time of KS diagnosis (KS-naive) with the corresponding data for 51 patients already receiving HAART at the time of KS diagnosis (KS-HAART). The analysis included all patients with a diagnosis of KS since January 1996 within two Italian cohorts of patients with human immunodeficiency virus. RESULTS: Immunologic and virologic status at the time of KS diagnosis were significantly more favorable in the KS-HAART group than in the KS-naive group. The frequency of cutaneous involvement was similar in both groups, but cutaneous disease was more indolent among KS-HAART patients, with 1 anatomic site of involvement in 9 patients (21%) and less than 10 lesions in 26 patients (60%), compared with 16 patients (12%; P = 0.06) and 47 patients (34%; P = 0.01), respectively, in the KS-naive group. A smaller proportion of KS-HAART patients presented with visceral disease (24% vs. 39%; P = 0.06); in particular, gastrointestinal tract involvement was significantly less frequent among KS-HAART patients (14%) compared with KS-naive patients (28%; P = 0.05). Median survival was not reached in either group, and the 3-year survival rates of KS-HAART patients (64%) and KS-naive patients (78%) were not significantly different. CONCLUSIONS: The data from the current study indicate that KS exhibits a less aggressive presentation in patients already receiving HAART compared with patients who are naive to HAART at KS diagnosis. Natural history and outcome do not appear to be influenced by the initiation of HAART before development of KS.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Therapeutic approaches to AIDS-related malignancies.

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relatively stability in the number of patients developing systemic NHL. AIDS related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non AIDS-defining tumors, such as Hodgkin's disease, anal and head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Hodgkin's disease in HIV.

The outcome of patients with HIV-HD has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs (ie, protease inhibitors), in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HD with chemotherapy. In fact, the possibility of reducing viral load to undetectable levels and increasing the CD4+ cell count reduces the risk of OIs during antineoplastic treatment. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HD may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. Finally, more effective antineoplastic regimens--such as high-dose chemotherapy with autologous stem cell transplantation (which is required in the case of HIV-HD, due to its aggressiveness)--should be considered to improve the response rate and disease-free survival of these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Idarubicin.

Explore the source record for details and available documents.

Administration, Oral↗
PubMedDate not supplied

Breast cancer and pregnancy.

The diagnosis of breast cancer during pregnancy is a rare event, but the young age of the patient together with the emotional impact for both the family and the doctors make therapeutic choices usually very difficult. Until recently, the occurrence of pregnancy associated breast cancer was thought to hold a grave prognosis and therapeutic abortion was very often advised in common practice. The hormonal environment with the increase in estrogens and progesterone was the main factor for the fear of tumor stimulation. The course of breast cancer, however, does not appear to be adversely affected by continuation of pregnancy. In the last years it was realized that potentially curative therapies can be administered even when pregnancy is continued. Of course in the medical literature there is no randomized clinical trial helping in taking decision in this setting; however, a significant experience already exists in some institutions and can guide management in these difficult cases. The aim of our review is to give an answer to questions usually coming from various specialists who collaborate with the oncologists in treating these patients and furthermore to try and find some basic guidelines which can be used in the information of the patients regarding previous experience in this field. The problem of a pregnancy after treatment for breast cancer is also analyzed, as this aspect is an emerging issue in clinical oncology. The decision should be evaluated for each single patient, taking into account the prognosis of the patient and her desire of pregnancy.

Breast Neoplasms↗
PubMedDate not supplied

Cisplatin may be a valid alternative approach in ovarian carcinoma with carboplatin hypersensitivity. Report of three cases.

Platinum-based therapy is considered the standard treatment for patients with advanced ovarian cancer. Carboplatin has a more favorable toxicity profile than cisplatin; however, hypersensitivity reactions to carboplatin have been reported occasionally. We reviewed 112 cases of ovarian cancer treated with carboplatin at our institute to identify the hypersensitivity reactions to this chemotherapeutic agent. Hypersensitivity reactions were documented in nine cases (8%). No deaths occurred, but the reactions were judged severe in three of the 112 patients (2.6%). In our own experience with patients showing idiosyncrasy to carboplatin we observed successful resolution after retreatment with cisplatin. Since patients who relapse after initial treatment with carboplatin often respond to it a second time, it is important to continue this treatment.

Adenocarcinoma↗
PubMedDate not supplied

Long-term survival in patients with metastatic renal cell carcinoma treated with continuous intravenous infusion of recombinant interleukin-2: the experience of a single institution.

AIM AND BACKGROUND: Metastatic renal cell carcinoma is one of the few tumors for which a clear benefit of immunotherapy has been demonstrated. The aim of this study was to evaluate the long-term survival of patients with metastatic renal cell carcinoma, along with response rate and other prognostic and predictive factors. PATIENTS AND METHODS: Between July 1989 and May 1995, 56 patients with metastatic renal cell carcinoma were treated in a single institution with high-dose recombinant interleukin-2 in continuous infusion. Survival was measured by the Kaplan and Meier method. Prognostic factors were assessed by univariate and multivariate analyses of survival (Cox proportional hazard ratio model). RESULTS: Of 56 patients, 15 had objective responses (26.8%), 16 stable disease (28.6%), 18 disease progressions (32.1%), and 7 (12.5%) were not valuable for response. Median overall survival was 20 months, and probability of 2- and 5-year survival was 41% and 21%, respectively. At multivariate analysis, the increased risk of death for: performance status > or = 2 vs 0 (HR = 6.20), stable disease (HR = 1.87), disease progression (HR = 10.61) vs partial or complete remission, and for hypotension and oliguria toxicity, G3 + G4 vs G1 + G2 (HR = 2.19). CONCLUSIONS: Our study confirms the activity of IL-2 based immunotherapy in renal cell carcinoma. Moreover, ECOG performance status, clinical response, hypotension and oliguria toxicity resulted as independent survival prognostic factors.

Aged↗