Patients currently taking metformin will be eligible Patients may not be taking metformin for a reason other than study participation Patients must not receive metformin for at least days prior to enrollment and for the duration of study treatment Subjects may have diabetes mellitus but must not be taking metformin Known hypersensitivity to metformin Subjects currently treated with metformin and/or bicalutamide or who have been treated with metformin and/or bicalutamide in the past months Prior or current use of metformin within the past months Subjects may have diabetes mellitus but must not be taking metformin or have previously taken metformin within previous year Subjects who are pregnant or breastfeeding, or may become pregnant during metformin and doxycycline administration Subjects on metformin or doxycycline for any reason during the preceding weeks Diabetic subjects that are managed by taking metformin or insulin Patient with prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past Patient is on medications that are contraindicated with metformin or doxycycline under current Food and Drug Administration (FDA) recommendations; the following is a list of medications identified as class D (consider therapy modification) when treatment with metformin or doxycycline is considered:\r\n* Class D:\r\n** Bismuth Subsalicylate\r\n** Cimetidine\r\n** Iodinated contrast agents\r\n** Somatropin Both arms: patients should not have received metformin within months prior to registration\r\n* Arm B: patients who were on metformin while on PD-/PD-L inhibitors are not eligible Patients must not have any of the following contraindications to metformin:\r\n* Hypersensitivity to metformin or any component of the formulation\r\n* Kidney dysfunction or abnormal creatinine (Cr < ng/mL) from any cause\r\n* Acute or metabolic acidosis Patients must be at least half-lives beyond previous treatment with metformin and currently not taking metformin History of hypersensitivity to TAK- or metformin Subjects who are pregnant or breastfeeding or may become pregnant during metformin and doxycycline administration Subjects on metformin or doxycycline for any reason during the preceding weeks Diabetic subjects are eligible if they are not taking metformin or insulin Prior allergic reaction to metformin, doxycycline, or any other tetracycline antibiotic in the past Patient is on medications that are contraindicated with metformin or doxycycline under current Food and Drug Administration (FDA) recommendations; the following is a list of medications identified as class D (consider therapy modification) when treatment with metformin or doxycycline is considered\r\n* Class D \r\n** Bismuth Subsalicylate\r\n** Cimetidine\r\n** Iodinated contrast agents\r\n** Somatropin Known sulfonylurea treatment within days prior to registration; sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); and glibornuride (Glutril) Patients who are currently taking metformin; prior metformin use is allowed if last dose was months previous to this trial Currently taking metformin, sulfonyureas, thiazolidenediones or insulin for any reason History of hypersensitivity to temsirolimus or metformin Subjects with known diabetes and those taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason Patients taking metformin or digoxin Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin Patients must NOT be taking metformin or have been on metformin in the past months Diabetic patients who are on metformin are eligible as long as they have been on metformin for less than months (estimated months or less duration of metformin therapy from start of metformin to enrollment on study) Current use of metformin for more than months prior to enrollment on study Patients who received aspirin or metformin within the past days Patients taking medications with known interactions with metformin or aspirin Currently taking metformin, sulfonylureas, thiazolidinediones, or insulin for any reason Have no contraindications to short-term metformin therapy Need to be able to undergo metformin treatment for a duration of weeks (+/- days) prior to repeat endometrial biopsy Are currently taking metformin or have taken metformin in the past months or have a history of an allergic reaction or intolerance at any time to metformin Are taking a drug that may significantly interact or influence the metabolism of metformin Prior metformin treatment OR EGFR targeted therapy Patients taking Metformin for any reason within days of enrollment to the study Subjects on metformin for any reason during the preceding weeks Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas Currently taking metformin, sulfonylureas, thiazolidinedione, insulin, or other antidiabetic drugs for any reason Patients already receiving metformin or anti-diabetic medications are INELIGIBLE Metformin use in the last months A known hypersensitivity to metformin Known intolerance to doxorubicin, metformin, or vincristine Patients who have a need to continue hydroxyurea while on study\r\n* Please note: patients may continue on hydroxyurea only until the first dose of metformin is to be given Known hypersensitivity to metformin or statins Patients currently treated with metformin or a statin or who have been treated with metformin or a statin in the past months are ineligible for this study Subjects on metformin for any reason during the preceding weeks Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas All medications other than those that may cause myelosuppression are permitted except those that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations Current metformin therapy Subjects who are pregnant or may become pregnant during metformin administration; pregnancy testing will be done in conjunction with preradiation protocols Subjects on metformin for any reason during the preceding weeks Diabetic subjects are eligible if they are not taking metformin or insulin All medications are permitted except those that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations Patients currently receiving or scheduled to receive a chemotherapy infusion other than adriamycin/cyclophosphamide prior to initiation of the metformin adaptation phase are not eligible; patients who are receiving adriamycin/cyclophosphamide must be scheduled to be at least days post-chemotherapy infusion prior to initiation of the metformin adaptation phase in order to be eligible Patients who are currently using metformin (eg, Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet) Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin Women who have taken metformin within the past days Currently taking medication that may impact weight (e.g., Synthroid, metformin) Current or prior regular use of metformin within the past months Current use of metformin or other anti-diabetic agents, or hypersensitivity or allergy to metformin Participants may not be using metformin, cimetidine (Tagamet), furosemide (Lasix), nifedipine (Cardizem), or any other drug contraindicated for use with metformin No current treatment with metformin, sulfonylureas, thiazolidinediones or insulin for any reason Prior treatment with metformin Known allergy to metformin or other biguanide (Proguanil) Participants who are taking metformin at the time of the exam are excluded Taking metformin (example: Glucophage, Glucovance, Avandamet, Metaglip) Currently taking Glucophage or Glucovance (metformin) NORMAL VOLUNTEERS: Be taking metformin, aminoglycosides, other nephrotoxic medications, or daily use of NSAIDs Patients with type diabetes mellitus (TDM) being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage XR, mg QD for days, then mg BID for - days) for a total of - days prior to surgery\r\n* Patients do not require a diagnosis of diabetes to be enrolled in the study All patients must be willing to keep a drug diary indicating the dates and times of metformin administration History of diabetes that is currently being treated without metformin Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period This criterion does not apply to patients taking clinically indicated metformin at the time of study entry Known hypersensitivity to metformin Must have been off metformin for at least weeks prior to starting IFN gamma Participants who are already on treatment with metformin, except when metformin can be held for weeks prior to the start of the study Diabetic patients are eligible but will be excluded if they are taking metformin, insulin or sulfonilureas