Patients must not have been treated with any of the following prior to step 1 initial registration:\r\n* Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR\r\n* HER-2 targeting for treatment of colorectal cancer; patients who have received prior trastuzumab or pertuzumab for other indications such as prior history of adjuvant or neoadjuvant breast cancer treatment prior to the development of advanced colorectal cancer are eligible Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer No prior chemotherapy for metastatic colorectal cancer Has pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma (until sponsor's notification to the study sites, subject must be a RAS/BRAF wild-type cancer) Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma. Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid. Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry) Must have previously treated metastatic colorectal cancer BRAF V600 mutant colorectal cancer Pathologically documented diagnosis of colorectal adenocarcinoma. Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic malignancy including multiple myeloma Pts with colorectal cancer must be KRAS wild-type Malignancies other than colorectal cancer within 5 years prior to Cycle 1 Day 1 Colorectal carcinoma (CRC). Currently receiving other systemic therapy for metastatic colorectal cancer COHORT B, GROUP 3: COLORECTAL CANCER: Patients must have colorectal adenocarcinoma that harbored a KRAS mutation COHORT B, GROUP 3: COLORECTAL CANCER: Patients must have failed a minimum of one previous line of chemotherapy Recurrent and/or metastatic unresectable colorectal cancer with hepatic metastases Metastatic colorectal cancer patients have progressed following at least one line of fluorouracil (5-FU)-based chemotherapy The study is intended to enroll patients with pancreatic and colorectal cancer; patients with other types of solid tumors will require approval by the principal investigator Patients previously treated with systemic chemotherapy and/or biologic agents for colorectal cancer are eligible Have histologically confirmed microsatellite stable metastatic colorectal cancer and have received at least one line of treatment for metastatic colorectal cancer including fluoropyrimidines, oxaliplatin and/or irinotecan Participants must have metastatic colorectal or pancreatic cancer Prior history of colorectal cancer PHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nHistologically or cytologically confirmed advanced colorectal cancer; patients must have progressed on, been intolerant of or refused prior oxaliplatin- and irinotecan-containing chemotherapeutic regimen, and have disease that is not amenable to potentially curative resection; patients who have a known KRAS (or NRAS or BRAF) wild type tumor must have progressed, been intolerant of or refused cetuximab or panitumumab-based chemotherapy Prior chemotherapy or radiotherapy for colorectal cancer Colorectal cancer Any prior systemic treatment for metastatic colorectal cancer Adjuvant systemic treatment for colorectal cancer within last 12 months Patients with colorectal cancer should have failed at least one oxaliplatin-containing regimen Subjects with advanced colorectal, gastric, hepatic or pancreatic cancer Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2). Subject is diagnosed with colorectal cancer Clinical diagnosis of appendiceal or colorectal neoplasm with peritoneal mucinosis or metastasis Part B: First-Line Colorectal Cancer Part B: Second-Line Colorectal Cancer Tumor blocks available from previous surgery/biopsy; at the tumor specific expansion, only patients with metastatic colorectal and renal cell cancers will be enrolled; patients with metastatic colorectal and renal cancer must have been treated and progressed or intolerant to standard care therapy; patients with colorectal cancer must have been treated in the past with irinotecan and/or oxaliplatin and/or avastin/EGFR therapy or intolerant to these agents; no more than 4 lines of therapy permitted in the metastatic setting; patients with colorectal cancer may enroll irrespective of K-Ras mutational status, although this will be documented; patients with renal cell cancer must have been treated with a VEGF targeted therapy and/or mTOR inhibitor; prior treatment with vorinostat and HCQ are not permitted in each tumor type Patients with wild-type or mutant Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC) Previous malignancy other than Colorectal cancer (CRC) in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix histopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal origin Must have started adjuvant FOLFOX chemotherapy within 8 weeks of resection for colorectal carcinoma 28 patients with refractory colorectal cancer. Prior systemic chemotherapy, immunotherapy (including interferon), or biological therapy, radiation therapy and/or surgery for resection of solid tumor (limited to: melanoma, kidney cancer, lung cancer, colorectal carcinoma, prostate cancer, and neuroendocrine tumor) are allowed. Kirsten rat sarcoma viral oncogene homolog (KRAS) mutated colorectal cancer Metatastic colorectal cancer Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid. Group 2: Patients with BRAF mutated colorectal cancer Metastatic colorectal cancer Family history of familial cancer syndromes (leukemia, breast, ovarian, colorectal, etc.) Patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless:\r\n* Either an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease, OR\r\n* The primary cancer was stage I\r\nClinicians should consider biopsy of lesions to establish the diagnosis of metastatic colorectal cancer in each case if there is substantial clinical ambiguity regarding the nature or source of apparent metastases Prior chemotherapy, other systemic therapy, or any investigational agent for treatment of advanced or metastatic colorectal cancer; patients who completed adjuvant or neoadjuvant chemotherapy > 12 months prior to colorectal cancer recurrence are eligible Part F: Colorectal Cancer Patients must have a primary L sided colorectal cancer (at or distal to the splenic flexure) Have a colorectal or coloanal reconstruction with or without reservoir/pouch. Advanced colorectal carcinoma. Patients must show signs of progression (by imaging, or tumor marker elevation) after being treated with a first line or greater treatment for their un-resectable or metastatic colorectal cancer CRC (Colorectal cancer): Patients with metastatic CRC and known KRAS (Kirsten rat sarcoma viral oncogene homolog) status who are eligible for treatment with regorafenib in accordance with the approved labeling. Have a history of Stage IV Colorectal Cancer (CRC) with metastases to the liver only Any prior treatment for metastatic colorectal cancer, except for use of palliative radiosensitizers Adjuvant chemotherapy for colorectal cancer completed < 12 months prior to study consent Evaluable or measurable radiographic evidence of colorectal cancer Patients with an obstructive synchronous colorectal tumor requiring up-front surgery or chemoradiation Has received at least 2 prior chemotherapeutic regimens for colorectal cancer; Diagnosed colorectal cancer with oligometastatic colorectal cancer in the lung Prior anti-cancer treatment for metastatic colorectal cancer Received any chemotherapeutic or targeted agent for metastatic colorectal cancer within two weeks of initiation of study drug Subjects with metastatic colorectal cancer may continue “maintenance” therapy with capecitabine and/or bevacizumab Colorectal cancer (for patients enrolled to expansion part) Prior treatment with taxane therapy for either colorectal cancer or small bowel adenocarcinoma Primary colorectal cancer diagnosis Prior chemotherapy for metastatic colorectal cancer is not allowed. Patients must have KRAS/NRAS/BRAF wild-type colorectal cancer Diagnosed with breast, colorectal, or prostate cancer (stages I-III) metastatic colorectal cancer (mCRC) that is microsatellite stable (MSS) Diagnosed with stage III or IV colorectal cancer Have been diagnosed with localized breast or prostate (stages 1-2) or colorectal cancer (stage 1-3) PHASE 0: Previously underwent curative surgical treatment of metastatic colorectal or peritoneal cancer at University of Pittsburgh Medical Center (UPMC) Shadyside PHASE 1 & 2: Scheduled for curative surgical treatment of metastatic colorectal or peritoneal cancer at UPMC Shadyside Diagnosed with stage 3 or 4 breast, cervical, colorectal, endometrial, hepatobiliary, lung, melanoma, gynecological, prostate cancer in the past six months Diagnosed with incurable (defined as metastatic or receiving chemotherapy with palliative intent) esophageal, gastric, pancreas, hepatobiliary, colorectal, or lung cancer within the prior 8 weeks (including patients with prior diagnosis of cancer who developed incurable disease) Scheduled to receive first-line intravenous chemotherapy treatment for colorectal cancer (stages II-IV) Patients with a primary diagnosis of either breast, lung, prostate, or colorectal cancer within the last two years Diagnosed with stage I-III colorectal cancer Within 12 months of completing active treatment for colorectal cancer Stage I-III colorectal cancer (CRC). Patient diagnosed with colorectal cancer Primary family caregivers of cancer patients with gastrointestinal (colorectal, pancreatic, gastric), gynecologic, urinary, or lung cancers who are entering the City of Hope for treatment or follow-up Patients with a history of other malignancies will not be excluded, as long as they are currently receiving treatment for lung, breast, colorectal, prostate, GYN, or other solid tumor cancer Histologically confirmed stage I-III colorectal or breast cancer who have undergone curative-intent complete surgical resection and completed all adjuvant cytotoxic chemotherapy and radiation (if indicated) at least 2 months prior to enrollment; breast cancer patients on hormonal therapy or trastuzumab only therapy and colorectal cancer patients on adjunctive therapies not considered cytotoxic chemotherapy (including those participating in Cancer and Leukemia Group B [CALGB] 80702 receiving only celecoxib/placebo) are eligible Scheduled to receive any form of further adjuvant cancer therapy (except hormonal or biologic therapy for breast cancer or adjunctive noncytotoxic chemotherapy for colorectal cancer including participation in CALGB 80702 while on celecoxib/placebo) Prisoners and individuals who are under the age of 18 will be specifically excluded from participation in the study; individuals must have a primary colorectal or endometrial cancer, not a recurrence of a previous colorectal or endometrial cancer Individuals with personal history of colorectal cancer (CRC) or colorectal polyps Have a first degree relative with a history of breast or colorectal cancer Outpatients scheduled for screening or surveillance colonoscopy for polyps or colorectal cancer ) Patients at high risk of colorectal cancer e.g. ulcerative colitis Patients must not have a known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease Diagnosis of colorectal adenoma of any grade Patients receiving prior chemotherapy or chemoradiation for colorectal cancer (ie, neoadjuvant chemoradiation for stage II or III rectal cancer) History of colorectal cancer; exception: individuals with stage I or II colorectal cancer who have not received any chemotherapy Chinese and Korean American patients who are not up to date for colorectal cancer screening Colorectal cancer At high risk of developing colorectal cancer, based upon a history of having a colonoscopy and having any colorectal adenoma diagnosed and/or removed within the past 3 years No history of colorectal cancer, including germ-line heritable colorectal cancers such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) History of at least one of the following conditions in the previous 12 months:\r\n* Colorectal adenoma(s) >= 1 cm in maximal diameter\r\n* Colorectal adenoma(s) with villous or tubulovillous histology\r\n* Colorectal adenoma(s) with high grade (severe) dysplasia History of any colorectal cancer History of heritable cancer syndrome (familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) Currently non-adherent to colorectal cancer screening Previously resected colorectal cancer Family history of polyposis syndrome (e.g., familial adenomatous polyposis [FAP], hereditary non-polyposis colorectal cancer [HNPCC]) or colorectal cancer (first degree relatives younger than 60 years old) History of difficulty with sigmoidoscopy or abnormal colorectal anatomy Diagnosed with primary or metastatic cancer in one or more of the following locations: breast, colorectal, lung, pancreas Received prior chemotherapy for colorectal cancer Participants with non-colorectal, non-gastric, or non-pancreatic cancer should have confirmed CEA expression in tumor tissue. CEA expression should be centrally confirmed. For colorectal cancer (CRC) participants, CEA assessment should be performed but the result is not required for participant selection. A pathologically documented colorectal cancer that: Have a primary diagnosis of non-metastatic colorectal cancer and have had surgery and are now receiving adjuvant chemotherapy Average-risk patients due for colorectal cancer (CRC) screening at the time of a primary care appointment who initiate a portal session within the two-week period following their visit Diagnosis of any stage I - IV colorectal cancer or recurrent colorectal cancer (Arm 1) Treat patients diagnosed with breast, prostate or colorectal cancer